研究者詳細 - 松崎　吾朗

論文 - 松崎　吾朗

分割表示 >> ／全件表示115 件中 1 - 115 件目

TAK1-binding protein 2 (TAB2) and TAB3 are redundantly required for TLR-induced cytokine production in macrophages

Ali, T; Nguyen, HM; Abbas, N; Takeuchi, O; Akira, S; Suzuki, T; Matsuzaki, G; Takaesu, G (担当範囲: 研究の企画、実験手技の指導。)

INTERNATIONAL IMMUNOLOGY 2024年04月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

TGF-β-activated kinase 1 (TAK1) plays a pivotal role in innate and adaptive immunity. TAK1 is essential for activating MAPK and NF-κB pathways downstream of the diverse immune receptors, including TLRs, cytokine receptors, TCR, and BCR. Upon stimulation, TAK1 is recruited to the lysine 63-linked poly-ubiquitin chain via TAK1-binding proteins (TAB)2 and TAB3. However, the physiological roles of TAB2 and TAB3 in the macrophages remain unclear. Ori et al. reported minor effects of TAB2/TAB3 double deficiency on TLR signaling in bone marrow-derived macrophages (BMDMs). However, the TAB2 conditional knockout (KO) mice used in their experimental system showed the residual TAB2 expression in BMDMs. In this study, we examined the roles of TAB2 and TAB3 in an improved KO mouse model. We observed a significant impairment in pro-inflammatory cytokine production in TAB2/TAB3 double KO (DKO) BMDMs but not in single KO BMDMs of either TAB2 or TAB3. Notably, upon TLR stimulation, IL-6 production was inhibited, whereas TNF-α production was partially reduced in the DKO BMDMs. Notably, TAB2 and TAB3 were nonessential in the TLR-induced TAK1 activation and exerted negligible effects on MAPK and NF-κB pathways. We observed that the TLR-mediated expression of IκBζ protein was severely compromised in the DKO BMDMs, which hindered IL-6 production. In contrast, the induction and the stability of IκBζ mRNA were comparable between the wild-type and DKO BMDMs. These results suggest that TAB2 and TAB3 play redundant and essential roles in regulating certain genes through TAK1-independent mechanisms in the TLR signaling pathway that are not yet known.

この論文にアクセスする

DOI
関連情報を調べる

PubMed

GRIM-19 is a target of mycobacterial Zn2+ metalloprotease 1 and indispensable for NLRP3 inflammasome activation.

Kurane T, Matsunaga T, Ida T, Sawada K, Nishimura A, , Fukui M, Umemura1 M, Nakayama M, Ohara N, Matsumoto S, Akaike T, Matsuzaki G, Takaesu G

FASEB Journal ( Wiley ) 36 ( 1 ) e22096 2022年10月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

関連する研究費コード: 20H03487

この論文にアクセスする

DOI
関連情報を調べる

PubMed CiNii Research

Heat-killed Lactobacillus plantarum L-137 attenuates obesity and associated metabolic abnormalities in C57BL/6 J mice on a high-fat diet.

Yoshitake R, Hirose Y, Murosaki S, Matsuzaki G.

Bioscience of Microbiota, Food and Health 40 ( 2 ) 84 - 91 2021年04月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

この論文にアクセスする

DOI

TREM2 is a receptor for non-glycosylated mycolic acids of mycobacteria that limits anti-mycobacterial macrophage activation.

Iizasa E, Chuma Y, Uematsu T, Kubota M, Kawaguchi H, Umemura M, Toyonaga K, Kiyohara H, Yano I, Colonna M, Sugita M, Matsuzaki G, Yamasaki S, Yoshida H, Hara H.

Nature Communications ( Nature Communications ) 12 ( 1 ) 2299 - 2299 2021年04月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

Mycobacterial cell-wall glycolipids elicit an anti-mycobacterial immune response via FcRγ-associated C-type lectin receptors, including Mincle, and caspase-recruitment domain family member 9 (CARD9). Additionally, mycobacteria harbor immuno-evasive cell-wall lipids associated with virulence and latency; however, a mechanism of action is unclear. Here, we show that the DAP12-associated triggering receptor expressed on myeloid cells 2 (TREM2) recognizes mycobacterial cell-wall mycolic acid (MA)-containing lipids and suggest a mechanism by which mycobacteria control host immunity via TREM2. Macrophages respond to glycosylated MA-containing lipids in a Mincle/FcRγ/CARD9-dependent manner to produce inflammatory cytokines and recruit inducible nitric oxide synthase (iNOS)-positive mycobactericidal macrophages. Conversely, macrophages respond to non-glycosylated MAs in a TREM2/DAP12-dependent but CARD9-independent manner to recruit iNOS-negative mycobacterium-permissive macrophages. Furthermore, TREM2 deletion enhances Mincle-induced macrophage activation in vitro and inflammation in vivo and accelerates the elimination of mycobacterial infection, suggesting that TREM2-DAP12 signaling counteracts Mincle-FcRγ-CARD9-mediated anti-mycobacterial immunity. Mycobacteria, therefore, harness TREM2 for immune evasion.

この論文にアクセスする

DOI
関連情報を調べる

PubMed

Mycobacterium bovis BCG-mediated suppression of Th17 response in mouse experimental autoimmune encephalomyelitis.

Matsuzaki G, Teruya N, Kiyohara Kohama H, Arai K, Shibuya Y, Chuma Y, Matsuo K.

Immunopharmacology and Immunotoxicology ( Informa UK Limited ) 42 ( 2 ) 203 - 211 2021年 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

INTRODUCTION: Multiple sclerosis (MS) is an autoimmune disease mediated by a pro-inflammatory immune response. Experimental autoimmune encephalomyelitis (EAE) induced by immunization of mice with a myelin oligodendrocyte glycoprotein (MOG) peptide emulsified in killed Mycobacterium tuberculosis-containing complete Freund's adjuvant (CFA-EAE) is used as a model of MS. Mycobacterium bovis BCG has been reported to ameliorate clinical symptoms of CFA-EAE, although the precise mechanism has not yet been documented. Since CFA-EAE uses adjuvant with mycobacterial antigens, mycobacterial antigen-specific T cells induced by CFA may cross-react with BCG and modulate EAE. METHODS: To exclude the influence of cross-reactivity, a modified murine EAE model (cell wall skeleton (CWS)-EAE) that does not induce mycobacterial antigen-specific T cells was established and used to reevaluate the therapeutic effects of BCG on EAE. RESULTS: Inoculation with BCG 6 d after CWS-EAE induction successfully ameliorated EAE symptoms, suggesting that the therapeutic effects of BCG are independent of the mycobacterial antigen-specific T cells induced by the CFA-EAE protocol. BCG inoculation into the CWS-EAE mice resulted in reduced levels of MOG-specific Th17 in the central nervous system (CNS) with reduced demyelinated lesions of the spinal cord. In the draining lymph nodes of the MOG-immunized sites, BCG inoculation resulted in an increase in MOG-specific Th17 and Th1 cells at an early stage of immune response. CONCLUSION: The results suggest that BCG inoculation suppresses the Th17 response in the CNS of EAE mice via a mechanism that may involve the suppression of egress of encephalitogenic T cells from lymphoid organs.

この論文にアクセスする

DOI
関連情報を調べる

PubMed CiNii Research

miR-935 inhibits oral squamous cell carcinoma and targets inositol polyphosphate-4-phophatase type IA (INPP4A).

Maruyama N, Umikawa M, Matsumoto H, Maruyma T, Nishihara K, Nakasone T, Matayoshi A, Goto T, Hirano F, Arasaki A, Nakamura H, Matsuzaki G, Takaesu G.

Anticancer Research ( Anticancer Research ) 40 ( 11 ) 6101 - 6113 2020年 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

この論文にアクセスする

DOI
関連情報を調べる

PubMed

Dispensable role of chemokine receptors in migration of mycobacterial antigen-specific CD4+ T cells into Mycobacterium-infected lung.

Matsuzaki G, Yamasaki M, Tamura T, Umemura M

Immunobiology ( Immunobiology ) 224 ( 3 ) 440 - 448 2019年05月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

この論文にアクセスする

DOI
関連情報を調べる

PubMed

Interleukin-17 family cytokines in protective immunity against infections: role of hematopoietic cell-derived and non-hematopoietic cell-derived interleukin-17s.

Matsuzaki G, Umemura M

Microbiology and immunology ( Microbiology and Immunology ) 62 ( 1 ) 1 - 13 2018年01月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

この論文にアクセスする

DOI
関連情報を調べる

PubMed

Two distinct ITAM-coupled receptors recognize mycobacterial mycolic acid-containing lipids and differently regulate immune responses

Ei'ichi Iizasa, Takayuki Uematsu, Yasushi Chuma, Hideyasu Kiyohara, Mio Kutobta, Masayuki Umemura, Goro Matsuzaki, Sho Yamasaki, Hiromitsu Hara

CYTOKINE ( ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD ) 100 26 - 27 2017年12月 [ 査読有り ]

掲載種別: 研究論文（その他学術会議資料等）

Involvement of IL-17A-producing TCR y delta T cells in late protective immunity against pulmonary Mycobacterium tuberculosis infection

Masayuki Umemura, Yuko Okamoto-Yoshida, Ayano Yahagi, Susumu Nakae, Yoichiro Iwakura, Giichi Takaesu, Goro Matsuzaki

JOURNAL OF IMMUNOLOGY ( AMER ASSOC IMMUNOLOGISTS ) 198 ( 1 ) 2017年05月 [ 査読有り ]

掲載種別: 研究論文（その他学術会議資料等）

C-Type Lectin Receptor DCAR Recognizes Mycobacterial Phosphatidyl-Inositol Mannosides to Promote a Th1 Response during Infection.

Toyonaga K, Torigoe S, Motomura Y, Kamichi T, Hayashi JM, Morita YS, Noguchi N, Chuma Y, Kiyohara H, Matsuo K, Tanaka H, Nakagawa Y, Sakuma T, Ohmuraya M, Yamamoto T, Umemura M, Matsuzaki G, Yoshikai Y, Yano I, Miyamoto T, Yamasaki S

Immunity ( Immunity ) 45 ( 6 ) 1245 - 1257 2016年12月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

この論文にアクセスする

DOI
関連情報を調べる

PubMed

Involvement of IL-17A-producing TCR γδ T cells in late protective immunity against pulmonary Mycobacterium tuberculosis infection.

Umemura M, Okamoto-Yoshida Y, Yahagi A, Touyama S, Nakae S, Iwakura Y, Matsuzaki G

Immunity, inflammation and disease ( Immunity Inflammation and Disease ) 4 ( 4 ) 401 - 412 2016年12月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

この論文にアクセスする

DOI
関連情報を調べる

PubMed

Recombinant Mycobacterium bovis bacillus Calmette-Guérin expressing Ag85B-IL-7 fusion protein enhances IL-17A-producing innate γδ T cells.

Hatano S, Tamura T, Umemura M, Matsuzaki G, Ohara N, Yoshikai Y

Vaccine ( Vaccine ) 34 ( 22 ) 2490 - 5 2016年05月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

この論文にアクセスする

DOI
関連情報を調べる

PubMed

Interleukin-22-Induced Antimicrobial Phospholipase A2 Group IIA Mediates Protective Innate Immunity of Nonhematopoietic Cells against Listeria monocytogenes.

Okita Y, Shiono T, Yahagi A, Hamada S, Umemura M, Matsuzaki G

Infection and immunity ( Infection and Immunity ) 84 ( 2 ) 573 - 9 2016年02月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

この論文にアクセスする

DOI
関連情報を調べる

PubMed

Regulation of innate immune response to mycobacteria through DAP12 versus FcR gamma-coupled myeloid receptors that recognize different mycolic acid-containing lipids

Iizasa E, Uematsu T, Kubota M, Kiyohara H, Chuma Y, Matsuzaki G, Yamasaki S, Yoshida H

European Journal of Immunology 46 1085 - 1086 2016年 [ 査読有り ]

掲載種別: 研究論文（その他学術会議資料等）

Enhanced effect of BCG vaccine against pulmonary Mycobacterium tuberculosis infection in mice with lung Th17 response to mycobacterial heparin-binding hemagglutinin adhesin antigen.

Fukui M, Shinjo K, Umemura M, Shigeno S, Harakuni T, Arakawa T, Matsuzaki G

Microbiology and immunology ( Microbiology and Immunology ) 59 ( 12 ) 735 - 43 2015年12月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

この論文にアクセスする

DOI
関連情報を調べる

PubMed

Angiopoietin-like protein 2 induces proinflammatory responses in peritoneal cells.

Umikawa M, Umikawa A, Asato T, Takei K, Matsuzaki G, Kariya K, Zhang CC

Biochemical and biophysical research communications ( Biochemical and Biophysical Research Communications ) 467 ( 2 ) 235 - 41 2015年11月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

この論文にアクセスする

DOI
関連情報を調べる

PubMed

IL-1 receptor antagonist-deficient mice develop autoimmune arthritis due to intrinsic activation of IL-17-producing CCR2(+)Vγ6(+)γδ T cells.

Akitsu A, Ishigame H, Kakuta S, Chung SH, Ikeda S, Shimizu K, Kubo S, Liu Y, Umemura M, Matsuzaki G, Yoshikai Y, Saijo S, Iwakura Y

Nature communications ( Nature Communications ) 6 7464 2015年06月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

この論文にアクセスする

DOI
関連情報を調べる

PubMed

Intravenous Mycobacterium Bovis Bacillus Calmette-Guérin Ameliorates Nonalcoholic Fatty Liver Disease in Obese, Diabetic ob/ob Mice.

Inafuku M, Matsuzaki G, Oku H

PloS one ( PLoS ONE ) 10 ( 6 ) e0128676 2015年 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

この論文にアクセスする

DOI
関連情報を調べる

PubMed

Enhancement of leptin receptor signaling by SOCS3 deficiency induces development of gastric tumors in mice.

Inagaki-Ohara K, Mayuzumi H, Kato S, Minokoshi Y, Otsubo T, Kawamura YI, Dohi T, Matsuzaki G, Yoshimura A

Oncogene ( Oncogene ) 33 ( 1 ) 74 - 84 2014年01月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

Leptin acts on its receptor (ObR) in the hypothalamus to inhibit food intake and energy expenditure. Leptin and ObR are also expressed in the gastrointestinal tract; however, the physiological significance of leptin signaling in the gut remains uncertain. Suppressor of cytokine signaling 3 (SOCS3) is a key negative feedback regulator of ObR-mediated signaling in the hypothalamus. We now show that gastrointestinal epithelial cell-specific SOCS3 conditional knockout (T3b-SOCS3 cKO) mice developed gastric tumors by enhancing leptin production and the ObRb/signal transducer and activator of transcription 3 (STAT3) signaling pathway. All T3b-SOCS3 cKO mice developed tumors in the stomach but not in the bowels by 2 months of age, even though the SOCS3 deletion occurred in both the epithelium of stomach and bowels. The tumors developed in the absence of the inflammatory response and all cKO mice died within 6 months. These tumors displayed pathology and molecular alterations, such as an increase in MUC2 (Mucin 2, oligomeric mucus/gel-forming) and TFF3 (trefoil factor 3), resembling human intestinal-type gastric tumors. Administration of antileptin antibody to T3b-SOCS3 cKO mice reduced hyperplasia of gastric mucosa, which is the step of the initiation of gastric tumor. These data suggest that SOCS3 is an antigastric tumor gene that suppresses leptin overexpression and ObRb/STAT3 hyperactivation, supporting the hypothesis that the leptin/ObRb/STAT3 axis accelerates tumorigenesis and that it may represent a new therapeutic target for the treatment of gastric cancer.

この論文にアクセスする

DOI
関連情報を調べる

PubMed

Innate and acquired immune responses to mycobacterial infections: involvement of IL-17A/IL-23 axis in protective immunity.

Umemura M, Matsuzaki G

Nihon Hansenbyo Gakkai zasshi = Japanese journal of leprosy : official organ of the Japanese Leprosy Association ( 日本ハンセン病学会 ) 82 ( 3 ) 123 - 32 2013年12月

掲載種別: 研究論文（学術雑誌）

未だに世界中の人々を死に至らしめる最も大きな原因は感染症であり、病原性マイコバクテリアの代表である結核菌の感染も再び猛威を拡げ、感染症研究に大きな期待が掛けられている。結核菌感染症のなかでも特に肺結核はその発症頻度が高く、しばしば致命的な疾患に陥るにもかかわらず、肺における感染防御メカニズムは不明瞭な点が多い。この結核菌に対する免疫監視メカニズムと結核菌の病原因子の相互作用を理解し、結核菌感染症における免疫応答の分子基盤を整理および再構築することが、免疫制御による結核の予防ならびに治療法の開発に繋がると考えられる。本稿では、結核菌感染症における病原体側あるいは宿主側の視点からの感染制御メカニズムを概説すると共に、最近注目されているIL-17A/IL-23系の役割について解説する。

この論文にアクセスする

DOI
関連情報を調べる

PubMed CiNii Research

A bio-nanocapsule containing envelope protein domain III of Japanese encephalitis virus protects mice against lethal Japanese encephalitis virus infection

Takeshi Miyata, Senji Tafuku, Tetsuya Harakuni, Masayuki Tadano, Nobuo Yoshimoto, Masumi Iijima, Hidenori Matsuo, Goro Matsuzaki, Shun'ichi Kuroda, Takeshi Arakawa

Microbiology and Immunology ( Wiley ) 57 ( 6 ) 470 - 477 2013年06月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

An engineered bio-nanocapsule (BNC) comprising modified hepatitis B surface antigen L protein was used as a physical scaffold for envelope protein domain III (D3) of Japanese encephalitis virus (JEV). At the N terminus, the BNC contained a two-tandem repeat of the Z domain (ZZ) derived from Staphylococcus aureus protein A (ZZ-BNC). The Lys-rich ZZ moiety exposed on the surface of ZZ-BNC was used for chemical conjugation with the JEV D3 antigen, which had been expressed and purified from Escherichia coli. Immunization of mice with D3 loaded on the surface of ZZ-BNC (ZZ-BNC:D3) augmented serum IgG response against JEV and increased protection against lethal JEV infection. The present study suggests that innocuous recombinant antigens, when loaded on the surface of ZZ-BNC, can be transformed to immunogenic antigens. © 2013 The Societies and Wiley Publishing Asia Pty Ltd.

この論文にアクセスする

DOI
関連情報を調べる

PubMed CiNii Research

A bio-nanocapsule containing envelope (E) protein domain III of Japanese encephalitis virus (JEV) protects mice against lethal JEV infection

Takeshi Miyata, Senji Tafuku, Tetsuya Harakuni, Masayuki Tadano, Nobuo Yoshimoto, Masumi Iijima, Hidenori Matsuo, Goro Matsuzaki, Shun'ichi Kuroda, Takeshi Arakawa

Microbiology and Immunology ( Wiley ) n/a - n/a 2013年04月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

この論文にアクセスする

DOI
関連情報を調べる

CiNii Research

Physicochemically stable cholera toxin B subunit pentamer created by peripheral molecular constraints imposed by de novo-introduced intersubunit disulfide crosslinks.

Miyata T, Oshiro S, Harakuni T, Taira T, Matsuzaki G, Arakawa T

Vaccine ( Vaccine ) 30 ( 28 ) 4225 - 32 2012年06月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

We attempted to generate a physicochemically stable cholera toxin B subunit (CTB) by de novo-introduction of intersubunit disulfide bonds between adjacent subunits. Genes encoding double mutant CTB (dmCTB) encompassing a pair of amino acids to be replaced with cysteine residues either at the N-terminal (T1C/T92C, Q3C/T47C), C-terminal (F25C/N103C, Y76C/N103C), or at the internal et-helix region (L77C/T78C), were engineered. One mutant with the N-terminal constraint [dmCTB(T1C/T92C)], expressed as pentamer retained monosialoganglioside G(M1) (GM1) binding affinity, and exhibited robust thermostability. However, when the mutant CTB was heat-treated in the presence of a reducing agent, the thermostable phenotype was abolished, indicating the observed phenotype is due to the introduction of intersubunit disulfide bonds. The mutant CTB also exhibited a strong acid stability at a pH as low as 1.2, as well as stability against incubation with sodium dodecyl sulfate at concentrations as high as 10%. Furthermore, intranasal administration of the mutant CTB to mice induced CTB-specific serum IgG even after heat treatment, while the wildtype CTB failed to show such heat-resistant mucosal immunogenicity. This study demonstrated that an enterotoxin B subunit could be transformed into a physicochemically stable pentamer by the de novo-introduction of peripherally arranged intersubunit disulfide crosslinks, which may prove to be a useful strategy for the development of molecularly stable enterotoxin B subunit-based vaccines and delivery molecules. (C) 2012 Elsevier Ltd. All rights reserved.

この論文にアクセスする

DOI
関連情報を調べる

PubMed

Inhibitory effects of an ellagic acid glucoside, okicamelliaside, on antigen-mediated degranulation in rat basophilic leukemia RBL-2H3 cells and passive cutaneous anaphylaxis reaction in mice.

Kuba-Miyara M, Agarie K, Sakima R, Imamura S, Tsuha K, Yasumoto T, Gima S, Matsuzaki G, Ikehara T

International immunopharmacology ( International Immunopharmacology ) 12 ( 4 ) 675 - 81 2012年04月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

Degranulation inhibitors in plants are widely used for prevention and treatment of immediate-type allergy. We previously isolated a new ellagic acid glucoside, okicamelliaside (OCS), from Camellia japonica leaves for use as a potent degranulation inhibitor. Crude extracts from leaves also suppressed allergic conjunctivitis in rats. In this study, we evaluated the in vivo effect of OCS using a pure sample and performed in vitro experiments to elucidate the mechanism underlying the extraordinary high potency of OCS and its aglycon. The IC50 values for degranulation of rat basophilic leukemia cells (RBL-2H3) were 14 nM for OCS and 3 mu M for aglycon, indicating that the two compounds were approximately 2 to 3 orders of magnitude more potent than the anti-allergic drugs ketotifen fumarate. DSCG, and tranilast (0.17, 3, and > 0.3 mM, respectively). Antigen-induced calcium ion (Ca2+) elevation was significantly inhibited by OCS and aglycon at all concentrations tested (p < 0.05). Upstream of the Ca2+ elevation in the principle signaling pathway, phosphorylation of Syk (Tyr525/526) and PLC gamma-1 (Tyr783 and Ser1248) were inhibited by OCS and aglycon. In DNA microarray-screening test, OCS inhibited expression of proinflammatory cytokines [interleukin (IL)-4 and IL-13], cytokine-producing signaling factors, and prostaglandin-endoperoxidase 2, indicating that OCS broadly inhibits allergic inflammation. During passive cutaneous anaphylaxis in mice, OCS significantly inhibited vascular hyperpermeability by two administration routes: a single intraperitoneal injection at 10 mg/kg and per os at 5 mg/kg for 7 days (p < 0.05). These results suggest the potential for OCS to alleviate symptoms of immediate-type allergy. (C) 2012 Elsevier B.V. All rights reserved.

この論文にアクセスする

DOI
関連情報を調べる

PubMed

Merozoite surface protein-1 of Plasmodium yoelii fused via an oligosaccharide moiety of cholera toxin B subunit glycoprotein expressed in yeast induced protective immunity against lethal malaria infection in mice.

Miyata T, Harakuni T, Taira T, Matsuzaki G, Arakawa T

Vaccine ( Vaccine ) 30 ( 5 ) 948 - 58 2012年01月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

Methylotrophic yeast (Pichia pastoris) secreted cholera toxin B subunit (CUB) predominantly as a biologically active pentamer (PpCTB) with identical ganglioside binding affinity profiles to that of choleragenoid. Unlike choleragenoid, however, the PpCTB did not induce a footpad edema response in mice. Of the two potential glycosylation sites (NIT4-6 and NICT90-92) for this protein, a N-linked oligosaccharide was identified at Asn4. The oligosaccharide, presumed to extend from the lateral circumference of the CUB pentamer ring structure, was exploited as a site-specific anchoring scaffold for the C-terminal 19-kDa merozoite surface protein-1 (MSP1-19) of the rodent malaria parasite, Plasmodium yoelii. Conjugation of MSP1-19 to PpCTB via its oligosaccharide moiety induced higher protective efficacy against lethal parasite infection than conjugation directly to the PpCTB protein body in both intranasal and subcutaneous immunization regimes. Such increased protection was potentially due to the higher antigen loading capacity of CUB achieved when the antigen was linked to the extended branches of the oligosaccharide. This might have allowed the antigen to reside in more spacious molecular environment with less steric hindrance between the constituent molecules of the fusion complex. (C) 2011 Elsevier Ltd. All rights reserved.

この論文にアクセスする

DOI
関連情報を調べる

PubMed

Interleukin-17A is involved in enhancement of tumor progression in murine intestine.

Oshiro K, Kohama H, Umemura M, Uyttenhove C, Inagaki-Ohara K, Arakawa T, Harada M, Nakae S, Iwakura Y, Nishimaki T, Matsuzaki G

Immunobiology ( Immunobiology ) 217 ( 1 ) 54 - 60 2012年01月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

Interleukin (IL)-17A is a cytokine involved in neutrophilic inflammation but the role of IL-17A in antitumor immunity is controversial because both pro- and anti-tumor activities of IL-17A have been reported. We hypothesized that constitutive expression of IL-17A in intestinal environment modifies tumor growth. To address the issue, mice were inoculated into subserosa of cecum (i.c.) with murine EL4 lymphoma expressing a model tumor antigen, and tumor growth was monitored. IL-17A-producing cells were detected both in tumor mass and in normal intestinal tissue of i.c. tumor-bearing wild type mice. Tumor size in the wild-type mice was significantly higher than that in the cecum of IL-17A gene-knockout mice. Furthermore, anti-IL-17A monoclonal antibody treatment of wild-type mice resulted in decreased tumor size in the cecum. Model tumor-antigen-specific interferon-gamma production was not modified in draining mesenteric lymph node cells in the absence or after neutralization of IL-17A. All the results suggest that constitutive expression of IL-17A in intestine enhances tumor growth, and anti-IL-17A antibody treatment is a candidate of a new anti-tumor immunotherapy against intestinal tumors. (C) 2011 Elsevier GmbH. All rights reserved.

この論文にアクセスする

DOI
関連情報を調べる

PubMed

Tricomponent immunopotentiating system as a novel molecular design strategy for malaria vaccine development.

Miyata T, Harakuni T, Tsuboi T, Sattabongkot J, Ikehara A, Tachibana M, Torii M, Matsuzaki G, Arakawa T

Infection and immunity ( American Society for Microbiology ) 79 ( 10 ) 4260 - 75 2011年10月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

<jats:title>ABSTRACT</jats:title> <jats:p> The creation of subunit vaccines to prevent malaria infection has been hampered by the intrinsically weak immunogenicity of the recombinant antigens. We have developed a novel strategy to increase immune responses by creating genetic fusion proteins to target specific antigen-presenting cells (APCs). The fusion complex was composed of three physically linked molecular entities: (i) a vaccine antigen, (ii) a multimeric α-helical coiled-coil core, and (iii) an APC-targeting ligand linked to the core via a flexible linker. The vaccine efficacy of the tricomponent complex was evaluated using an ookinete surface protein of <jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Plasmodium vivax</jats:named-content> , Pvs25, and merozoite surface protein-1 of <jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Plasmodium yoelii</jats:named-content> . Immunization of mice with the tricomponent complex induced a robust antibody response and conferred substantial levels of <jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">P. vivax</jats:named-content> transmission blockade as evaluated by a membrane feed assay, as well as protection from lethal <jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">P. yoelii</jats:named-content> infection. The observed effect was strongly dependent on the presence of all three components physically integrated as a fusion complex. This system, designated the tricomponent immunopotentiating system (TIPS), onto which any recombinant protein antigens or nonproteinaceous substances could be loaded, may be a promising strategy for devising subunit vaccines or adjuvants against various infectious diseases, including malaria. </jats:p>

この論文にアクセスする

DOI
関連情報を調べる

PubMed CiNii Research

[Interleukin network in pulmonary tuberculosis].

Matsuzaki G, Umemura M

Nihon rinsho. Japanese journal of clinical medicine ( 日本臨床社 ) 69 ( 8 ) 1368 - 1372 2011年08月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

関連情報を調べる

PubMed

[Interleukin network in pulmonary tuberculosis].

Matsuzaki G, Umemura M

Nihon rinsho. Japanese journal of clinical medicine 69 ( 8 ) 1368 - 72 2011年08月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

関連情報を調べる

PubMed

Contribution of IL-17–producing γδ T cells to the efficacy of anticancer chemotherapy

Yuting Ma, Laetitia Aymeric, Clara Locher, Stephen R. Mattarollo, Nicolas F. Delahaye, Pablo Pereira, Laurent Boucontet, Lionel Apetoh, François Ghiringhelli, Noëlia Casares, Juan José Lasarte, Goro Matsuzaki, Koichi Ikuta, Bernard Ryffel, Kamel Benlagha, Antoine Tesnière, Nicolas Ibrahim, Julie Déchanet-Merville, Nathalie Chaput, Mark J. Smyth, Guido Kroemer, Laurence Zitvogel

Journal of Experimental Medicine ( Rockefeller University Press ) 208 ( 3 ) 491 - 503 2011年03月

掲載種別: 研究論文（学術雑誌）

<jats:p>By triggering immunogenic cell death, some anticancer compounds, including anthracyclines and oxaliplatin, elicit tumor-specific, interferon-γ–producing CD8+ αβ T lymphocytes (Tc1 CTLs) that are pivotal for an optimal therapeutic outcome. Here, we demonstrate that chemotherapy induces a rapid and prominent invasion of interleukin (IL)-17–producing γδ (Vγ4+ and Vγ6+) T lymphocytes (γδ T17 cells) that precedes the accumulation of Tc1 CTLs within the tumor bed. In T cell receptor δ−/− or Vγ4/6−/− mice, the therapeutic efficacy of chemotherapy was compromised, no IL-17 was produced by tumor-infiltrating T cells, and Tc1 CTLs failed to invade the tumor after treatment. Although γδ T17 cells could produce both IL-17A and IL-22, the absence of a functional IL-17A–IL-17R pathway significantly reduced tumor-specific T cell responses elicited by tumor cell death, and the efficacy of chemotherapy in four independent transplantable tumor models. Adoptive transfer of γδ T cells restored the efficacy of chemotherapy in IL-17A−/− hosts. The anticancer effect of infused γδ T cells was lost when they lacked either IL-1R1 or IL-17A. Conventional helper CD4+ αβ T cells failed to produce IL-17 after chemotherapy. We conclude that γδ T17 cells play a decisive role in chemotherapy-induced anticancer immune responses.</jats:p>

この論文にアクセスする

DOI
関連情報を調べる

PubMed CiNii Research

Interleukin-17A is required to suppress invasion of Salmonella enterica serovar Typhimurium to enteric mucosa.

Mayuzumi H, Inagaki-Ohara K, Uyttenhove C, Okamoto Y, Matsuzaki G

Immunology ( Immunology ) 131 ( 3 ) 377 - 85 2010年11月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

P>Salmonella enterica serovar Typhimurium (S. typhimurium) causes a localized enteric infection and its elimination is dependent on a T helper type 1 immune response. However, the mechanism of the protective immune response against the pathogen in gut-associated lymphoid tissue (GALT) at an early stage of the infection is not yet clarified. Here, we show that interleukin-17A (IL-17A) was constitutively expressed in GALT; it was also detected on crypt and epithelial cells of the small intestine. Neutralization of the IL-17A in the intestinal lumen exacerbated epithelial damage induced by intestinal S. typhimurium infection at an early stage of the infection. The result suggests that IL-17A has a pivotal role in the immediate early stage of protection against bacterial infection at the intestinal mucosa. As IL-17A neutralization also suppressed the constitutive localization of beta-defensin 3 (BD3), an IL-17A-induced antimicrobial peptide, at the apical site of the intestinal mucosa, it is estimated that IL-17A constitutively induces the expression of the antimicrobial peptide to kill invading pathogens at the epithelial surface immediately after the infection. In contrast, interferon-gamma is induced around 3 days after S. typhimurium infection, and its expression level increases thereafter. Taken together, the findings lead to the hypothesis that IL-17A participates in the immediate early stage of protection against S. typhimurium intestinal infection whereas interferon-gamma is important at a later stage of the infection.

この論文にアクセスする

DOI
関連情報を調べる

PubMed

Plasmodium vivax ookinete surface protein Pvs25 linked to cholera toxin B subunit induces potent transmission-blocking immunity by intranasal as well as subcutaneous immunization.

Miyata T, Harakuni T, Tsuboi T, Sattabongkot J, Kohama H, Tachibana M, Matsuzaki G, Torii M, Arakawa T

Infection and immunity ( American Society for Microbiology ) 78 ( 9 ) 3773 - 82 2010年09月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

<jats:title>ABSTRACT</jats:title> <jats:p> The nontoxic cholera toxin B subunit (CTB) was evaluated as a potential delivery molecule for the <jats:italic>Plasmodium vivax</jats:italic> ookinete surface protein, Pvs25. Recombinant Pvs25 was expressed as a secreted protein in the yeast <jats:italic>Pichia pastoris</jats:italic> , as a mixture of isoforms including multimers and the A and B monomers. The A isoform with the presumed native protein fold was the most abundant, accounting for more than 40% of all expressed protein. The molecularly uniform A isoform was chemically conjugated to CTB via its primary amines, and the fusion protein, retaining GM1-ganglioside affinity, was administered to BALB/c mice by the subcutaneous (s.c.) or intranasal (i.n.) route. Immunization of mice with conjugated Pvs25 without supplemental adjuvant induced antisera that specifically recognized <jats:italic>P. vivax</jats:italic> ookinetes <jats:italic>in vitro</jats:italic> . Furthermore, the antisera, when mixed with parasitized blood isolated from <jats:italic>P. vivax</jats:italic> patients from Thailand, was found to reduce parasite transmission to mosquitoes, conferring a 93 to 98% (s.c.) or a 73 to 88% (i.n.) decrease in oocyst number. Unconjugated Pvs25 alone conferred only a 23 to 60% (s.c.) or a 0 to 6% (i.n.) decrease in oocyst number. Coadministration of extraneous adjuvants, however, further enhanced the vaccine efficacy up to complete blockade. Taken together, we conclude that a weakly immunogenic Pvs25 by itself, when linked to CTB, transforms into a potent transmission-blocking antigen in both i.n. and s.c. routes. In addition, the present study is, to the best of our knowledge, the first demonstration of the immune potentiating function of CTB for a vaccine antigen delivered by the s.c. route. </jats:p>

この論文にアクセスする

DOI
関連情報を調べる

PubMed CiNii Research

Essential role of IL-17A in the formation of a mycobacterial infection-induced granuloma in the lung.

Okamoto Yoshida Y, Umemura M, Yahagi A, O'Brien RL, Ikuta K, Kishihara K, Hara H, Nakae S, Iwakura Y, Matsuzaki G

Journal of immunology (Baltimore, Md. : 1950) ( The American Association of Immunologists ) 184 ( 8 ) 4414 - 22 2010年04月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

<jats:title>Abstract</jats:title> <jats:p>Granulomas play an essential role in the sequestration and killing of mycobacteria in the lung; however, the mechanisms of their development and maturation are still not clearly understood. IL-17A is involved in mature granuloma formation in the mycobacteria-infected lung. Therefore, IL-17A gene-knockout (KO) mice fail to develop mature granulomas in the Mycobacterium bovis bacille Calmette-Guérin (BCG)-infected lung. This study analyzed the mechanism of IL-17A–dependent mature granuloma formation in the mycobacteria-infected lung. The IL-17A KO mice showed a normal level of nascent granuloma formation on day 14 but failed to develop mature granulomas on day 28 after the BCG infection in the lung. The observation implies that IL-17A is required for the maturation of granuloma from the nascent to mature stage. TCR γδ T cells expressing TCR Vγ4 or Vγ6 were identified as the major IL-17A–producing cells that resided in the BCG-induced lung granuloma. The adoptive transfer of the IL-17A–producing TCR γδ T cells reconstituted granuloma formation in the IL-17A KO mice. The expression of ICAM-1 and LFA-1, which are adhesion molecules important in granuloma formation, decreased in the lung of the BCG-infected IL-17A KO mice, and their expression was induced on BCG-infected macrophages in coculture with IL-17A–producing TCR γδ T cells. Furthermore, IL-17A KO mice showed not only an impaired mature granuloma formation, but also an impaired protective response to virulent Mycobacterium tuberculosis. Therefore, IL-17A produced by TCR γδ T cells plays a critical role in the prevention of M. tuberculosis infection through the induction of mature granuloma formation.</jats:p>

この論文にアクセスする

DOI
関連情報を調べる

PubMed CiNii Research

Suppressed induction of mycobacterial antigen-specific Th1-type CD4+ T cells in the lung after pulmonary mycobacterial infection.

Yahagi A, Umemura M, Tamura T, Kariyone A, Begum MD, Kawakami K, Okamoto Y, Hamada S, Oshiro K, Kohama H, Arakawa T, Ohara N, Takatsu K, Matsuzaki G

International immunology ( International Immunology ) 22 ( 4 ) 307 - 18 2010年04月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

Although the importance of T(h)1-type immune response in protection against mycobacterial infection is well recognized, its regulatory mechanism in the Mycobacterium tuberculosis (Mtb)-infected lung is not well characterized. To address this issue, we analyzed kinetics of induction of mycobacterial antigen-specific CD4(+) T(h)1 T cells after mycobacterial infection in P25 TCR-transgenic (Tg) mice which express TCR alpha and beta chains from a mycobacterial Ag85B-specific MHC class II A(b)-restricted CD4(+) T-cell clone. To supply normal regulatory T-cell repertoire, we transferred normal spleen T cells into the P25 TCR-Tg mice before infection. High dose subcutaneous infection with Mtb or Mycobacterium bovis bacillus Calmette-Guerin (BCG) induced P25 TCR-Tg CD4(+) T(h)1 cells within a week. In contrast, high-dose Mtb or BCG infection into the lung failed to induce P25 TCR-Tg CD4(+) T(h)1 cells at the early stage of the infection. Furthermore, low-dose Mtb infection into the lung induced P25 TCR-Tg CD4(+) T(h)1 cells on day 21 in the mediastinal lymph node but not in the lung. IL-10 was partially involved in the suppression of T(h)1 induction in the lung because pretreatment of mice with anti-IL-10 antibody resulted in increase of P25 TCR-Tg CD4(+) T(h)1 cells in the Mtb-infected lung on day 21 of the infection, whereas neutralization of transforming growth factor-beta, another important suppressive cytokine in the lung, showed no effects on the T(h)1 induction. Our data suggest that induction of anti-mycobacterial CD4(+) T(h)1 cells is suppressed in the mycobacteria-infected lung partially by IL-10.

この論文にアクセスする

DOI
関連情報を調べる

PubMed

Accelerated induction of mycobacterial antigen-specific CD8+ T cells in the Mycobacterium tuberculosis-infected lung by subcutaneous vaccination with Mycobacterium bovis bacille Calmette-Guérin.

Begum D, Umemura M, Yahagi A, Okamoto Y, Hamada S, Oshiro K, Matsuzaki G

Immunology ( Immunology ) 128 ( 4 ) 556 - 563 2009年12月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

P>Both CD4+ and CD8+ T cells are important in protection against Mycobacterium tuberculosis infection. To evaluate the effect of vaccination with Mycobacterium bovis bacille Calmette-Guerin (BCG) on the CD8+ T-cell response to pulmonary M. tuberculosis infection, we analyzed the kinetics of CD8+ T cells specific to the mycobacterial Mtb32a(309-318) epitope, which is shared by M. tuberculosis and M. bovis BCG, in the lung of mice infected with M. tuberculosis. The CD8+ T cells were detected by staining lymphocytes with pentameric major histocompatibility complex (MHC) class I H-2Db-Mtb32a(209-318) peptide complex and were analysed by flow cytometry. Mtb32a-specific CD8+ T cells became detectable on day 14, and reached a plateau on day 21, in the lung of M. tuberculosis-infected unvaccinated mice. Subcutaneous vaccination with M. bovis BCG in the footpads induced Mtb32a-specific CD8+ T cells in the draining lymph nodes (LNs) on day 7 and their numbers further increased on day 14. When M. bovis BCG-vaccinated mice were exposed to pulmonaryinfection with M. tuberculosis 4 weeks after vaccination, the Mtb32a-specific CD8+ T cells in the infected lung became detectable on day 7 and reached a plateau on day 14, which was 1 week earlier than in the unvaccinated mice. The pulmonary CD8+ T cells from the BCG-vaccinated M. tuberculosis-infected mice produced interferon-gamma in response to Mtb32a(209-318) peptide on day 7 of the infection, whereas those of unvaccinated mice did not. The results demonstrate that induction of mycobacterial antigen-specific protective CD8+ T cells in the M. tuberculosis-infected lung is accelerated by subcutaneous vaccination with M. bovis BCG.

この論文にアクセスする

DOI
関連情報を調べる

PubMed

Importance of murine Vdelta1gammadelta T cells expressing interferon-gamma and interleukin-17A in innate protection against Listeria monocytogenes infection.

Hamada S, Umemura M, Shiono T, Hara H, Kishihara K, Tanaka K, Mayuzumi H, Ohta T, Matsuzaki G

Immunology ( Immunology ) 125 ( 2 ) 170 - 7 2008年10月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

Murine gamma delta T cells participate in the innate immune response against infection by an intracellular pathogen Listeria monocytogenes. V delta 1(+)gamma delta T cells coexpressing V gamma 6 are a major gamma delta T-cell subpopulation induced at an early stage of L. monocytogenes infection in the livers of infected mice. To investigate the protective role of the V gamma 6/V delta 1(+)gamma delta T cells against L. monocytogenes infection, V delta 1 gene-deficient (V delta 1(-/-)) mice were analysed because these mice selectively lacked a V gamma 6/V delta 1(+)gamma delta T-cell subpopulation in the L. monocytogenes-infected liver. The V delta 1(-/-) mice showed increased bacterial burden in the liver and spleen, and decreased survival rate at an early stage of L. monocytogenes infection when compared to wild-type mice. Histological examination showed abscess-like lesions and unorganized distribution of macrophages in the liver of the V delta 1(-/-) mice but not in the wild-type mice after L. monocytogenes infection. The V gamma 6/V delta 1(+)gamma delta T cells produced interferon-gamma and interleukin-17A. All the results suggest that murine V gamma 6/V delta 1(+)gamma delta T cells control the innate protective response against L. monocytogenes infection through production of the proinflammatory cytokines interferon-gamma and interleukin-17A in the infected liver.

この論文にアクセスする

DOI
関連情報を調べる

PubMed

IL-17A produced by gammadelta T cells plays a critical role in innate immunity against listeria monocytogenes infection in the liver.

Satoru Hamada, Masayuki Umemura, Takeru Shiono, Kensho Tanaka, Ayano Yahagi, M Dilara Begum, Kiyotetsu Oshiro, Yuko Okamoto, Hisami Watanabe, Kazuyoshi Kawakami, Christina Roark, Willi K Born, Rebecca O'Brien, Koichi Ikuta, Hiromichi Ishikawa, Susumu Nakae, Yoichiro Iwakura, Takao Ohta, Goro Matsuzaki

Journal of immunology (Baltimore, Md. : 1950) 181 ( 5 ) 3456 - 63 2008年09月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

IL-17A is originally identified as a proinflammatory cytokine that induces neutrophils. Although IL-17A production by CD4(+) Th17 T cells is well documented, it is not clear whether IL-17A is produced and participates in the innate immune response against infections. In the present report, we demonstrate that IL-17A is expressed in the liver of mice infected with Listeria monocytogenes from an early stage of infection. IL-17A is important in protective immunity at an early stage of listerial infection in the liver because IL-17A-deficient mice showed aggravation of the protective response. The major IL-17A-producing cells at the early stage were TCR gammadelta T cells expressing TCR Vgamma4 or Vgamma6. Interestingly, TCR gammadelta T cells expressing both IFN-gamma and IL-17A were hardly detected, indicating that the IL-17A-producing TCR gammadelta T cells are distinct from IFN-gamma-producing gammadelta T cells, similar to the distinction between Th17 and Th1 in CD4(+) T cells. All the results suggest that IL-17A is a newly discovered effector molecule produced by TCR gammadelta T cells, which is important in innate immunity in the liver.

関連情報を調べる

PubMed

Rapid induction of OX40 ligand on primary T cells activated under DNA-damaging conditions.

Kondo K, Okuma K, Tanaka R, Matsuzaki G, Ansari AA, Tanaka Y

Human immunology ( Human Immunology ) 69 ( 9 ) 533 - 42 2008年09月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

We have previously demonstrated that normal human T cells either tong-term repeatedly stimulated or freshly activated in vitro in the presence of TGF-beta express the cell surface T-cell costimulating molecule OX40 ligand (OX40L). To further elucidate the kinetics of OX40L expression by human T cells, we have examined whether cell proliferation was required for the expression of CX40L. Thus, normal fresh peripheral blood mononuclear cells were stimulated with immobilized anti-CD3 antibody in the presence of the DNA synthesis-blocking agents such as mitomycin C, 5-fluorouracil, or X-ray irradiation. Flow cytometric analyses demonstrated that a significant frequency of these DNA-damaged activated primary CD4(+) and CD8(+) T cells became OX40L(+) as early as 1 hour after treatment. The OX40L induction on the DNA-damaged activated T cells was inhibited by treatment with either RNA or protein synthesis inhibitors, actinomycin D, or cycloheximide, respectively. Induced OX40L on T cells was functional because it bound recombinant OX40. These data indicate that human primary T cells are programmed to rapidly express functional OX40L molecules after stimulation under DNA-damaging conditions, demonstrating that the induction of OX40L by T cells is independent of cell proliferation. The clinical implications of these new findings are discussed. (C) 2008 American Society for Histocompatibitity and Immunogenetics. Published by Elsevier Inc. All rights reserved.

この論文にアクセスする

DOI
関連情報を調べる

PubMed

Mucosal immunization with recombinant heparin-binding haemagglutinin adhesin suppresses extrapulmonary dissemination of Mycobacterium bovis bacillus Calmette-Guérin (BCG) in infected mice.

Kohama H, Umemura M, Okamoto Y, Yahagi A, Goga H, Harakuni T, Matsuzaki G, Arakawa T

Vaccine ( Vaccine ) 26 ( 7 ) 924 - 32 2008年02月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

It is generally accepted that cellular immunity plays a critical role in the protection against Mycobacterium tuberculosis, an intracellular pathogen. Recently, however, an increasing number of reports indicate the important contribution of humoral immunity against mycobacterial infection. Since M. tuberculosis establishes its primary lesion in the lung, induction of humoral immunity in the airway tract by mucosal immunization regime could provide protective immunity against tuberculosis. In this study, mycobacterial heparin-binding haemagglutinin adhesin (HBHA) was used as an immunization antigen because HBHA is an essential virulence factor required for the infection of lung epithelial cells and extrapulmonary dissemination of mycobacteria. The effects of intranasal immunization with a yeast-expressed recombinant (r) HBHA co-administered with a mucosal adjuvant cholera toxin (CT) on the induction of humoral and cellular immunity were examined, and its protective efficacy against pulmonary challenge infection with Mycobacterium bovis bacillus Calmette-Guérin (BCG) was evaluated. HBHA-specific antibodies were induced in serum and airway tract of immunized mice, which specifically recognized native HBHA expressed on M. bovis BCG. Th1-type immunity against mycobacterial antigens was also enhanced in the lung of immunized mice after pulmonary BCG infection. Furthermore, the immunization suppressed bacterial load in the spleen after pulmonary BCG infection. These results indicate that systemic and local humoral immunity induced by the HBHA-based mucosal vaccine impairs extrapulmonary dissemination, thus providing immune protection against mycobacterial infection.

この論文にアクセスする

DOI
関連情報を調べる

PubMed

In Vivo Analysis of the Anti-allergic Activities of Camellia japonica Extract and Okicamelliaside, a Degranulation Inhibitor

Kuba Megumi, Tsuha Kazuyo, Tsuha Keiko, MATSUZAKI Goro, YASUMOTO Takeshi

ＪＯＵＲＮＡＬ　ＯＦ　ＨＥＡＬＴＨ　ＳＣＩＥＮＣＥ ( 公益社団法人日本薬学会 ) 54 ( 5 ) 584 - 588 2008年 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

Based on the previous finding of okicamelliaside (OCS), a highly potent anti-degranulation ellagic acid glucoside, in the leaves of Camellia japonica (C. japonica), we evaluated an extract of these leaves and OCS itself for their potential to suppress allergic reactions in vivo. Two conventional animal allergy models were used. In the allergic conjunctivitis model, male S.D. rats were stimulated with anti-ovalbumin (OVA) serum and challenged with OVA/Evans blue mixture. Oral administration of extracts from C. japonica at 1000 mg/kg for 10 days significantly reduced the vascular permeability of conjunctivas. In the second model, male BALB/c mice were stimulated with a Japanese cedar pollen extract and challenged by nasal instillation of the antigen. The sneezing frequency during the 10 min immediately after the challenge tended to decrease by intraperitoneal administration of 0.2 mg/kg of OCS for 24 days. These results suggest that C. japonica extracts (CJE) and OCS prepared from them could be useful to alleviate the symptoms of an immediate-type allergy.

この論文にアクセスする

DOI
関連情報を調べる

CiNii Research

IL-17-mediated regulation of innate and acquired immune response against pulmonary Mycobacterium bovis bacille Calmette-Guerin infection.

Umemura M, Yahagi A, Hamada S, Begum MD, Watanabe H, Kawakami K, Suda T, Sudo K, Nakae S, Iwakura Y, Matsuzaki G

Journal of immunology (Baltimore, Md. : 1950) ( The American Association of Immunologists ) 178 ( 6 ) 3786 - 96 2007年03月

掲載種別: 研究論文（学術雑誌）

<jats:title>Abstract</jats:title> <jats:p>IL-17 is a cytokine that induces neutrophil-mediated inflammation, but its role in protective immunity against intracellular bacterial infection remains unclear. In the present study, we demonstrate that IL-17 is an important cytokine not only in the early neutrophil-mediated inflammatory response, but also in T cell-mediated IFN-γ production and granuloma formation in response to pulmonary infection by Mycobacterium bovis bacille Calmette-Guérin (BCG). IL-17 expression in the BCG-infected lung was detected from the first day after infection and the expression depended on IL-23. Our observations indicated that γδ T cells are a primary source of IL-17. Lung-infiltrating T cells of IL-17-deficient mice produced less IFN-γ in comparison to those from wild-type mice 4 wk after BCG infection. Impaired granuloma formation was also observed in the infected lungs of IL-17-deficient mice, which is consistent with the decreased delayed-type hypersensitivity response of the infected mice against mycobacterial Ag. These data suggest that IL-17 is an important cytokine in the induction of optimal Th1 response and protective immunity against mycobacterial infection.</jats:p>

この論文にアクセスする

DOI
関連情報を調べる

PubMed CiNii Research

結核菌の肺感染局所における免疫システムの解明と新たなワクチン開発への応用

新川　武,梅村　正幸

研究報告書（遺伝子実験センター） ( 松﨑吾朗 ) 2007年03月

掲載種別: 研究論文（その他学術会議資料等）

平成16-17年度科学研究費補助金(基盤研究(C))研究成果報告書 / 研究概要：本研究では、肺結核における肺での免疫応答誘導機構を検討するために、結核菌抗原Ag85B特異的CD4陽性T細胞のT細胞抗原レセプター遺伝子を発現するトランスジェニック(P25-TCRTg)マウスを用いた実験系を確立した。無処置のP25-TCR TgマウスのT細胞は、ほぼ全てが結核菌抗原特異的なナイーブT細胞であるため、このT細胞を養子移入した宿主マウスに結核菌を肺感染させた後に移入T細胞を追跡すれば、肺におけるT細胞活性化過程がモニターできる。この方法により結核菌肺感染後の肺及び肺所属リンパ節における結核菌特異的T細胞の動態・活性化及びインターフェロンγ(IFN-γ)産生を検討した。その結果、肺・リンパ節ともに結核菌抗原特異的T細胞の増加および活性化マーカーCD69発現増加が同様な経過で認められたが、細胞内IFN-γ発現は、肺でのみ選択的に強く検出された。従って、肺における免疫応答の誘導は、必ずしも所属リンパ節の免疫応答とは平行しないことが示唆された。上記の実験系では、検出されるTgT細胞数が非常に少なく明瞭な解析が困難であった。この点を改善するためにP25-TCR Tgマウスに正常T細胞を移入するという逆の移入実験を行なった。これにより、大多数のT細胞がP25-TCR TgT細胞であるが、その他の特殊なT細胞(例えばNKT細胞など)も存在するマウスが作成される。このマウスに結核菌を肺感染させた場合も、肺・リンパ節とも感染後に結核菌抗原特異的T細胞の増加・活性化マーカーの獲得が明瞭に検出されたが、IFN-γ産生は肺においてのみ強く認められ、上記の仮説が支持された。今後は、これらの実験系を用いて、結核感染時に肺と所属リンパ節との間で認められた獲得免疫誘導の乖離のメカニズムを詳細に解析するとともに、この実験系を組換え結核抗原ワクチンの効果検討に応用する。（管理者追加）リポジトリ登録情報を移行しました。確認のうえ、加除修正をしてください。

この論文にアクセスする

DOI

IL-17-mediated regulation of innate and acquired immune response against pulmonary Mycobacterium bovis bacille Calmette-Guerin infection

Masayuki Umemura, Ayano Yahagi, Satoru Hamada, Mst Dilara Begum, Hisami Watanabe, Kazuyoshi Kawakami, Takashi Suda, Katsuko Sudo, Susumu Nakae, Yoichiro Iwakura, Goro Matsuzaki

JOURNAL OF IMMUNOLOGY ( AMER ASSOC IMMUNOLOGISTS ) 178 ( 6 ) 3786 - 3796 2007年03月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

IL-17 is a cytokine that induces neutrophil-mediated inflammation, but its role in protective immunity against intracellular bacterial infection remains unclear. In the present. study; we demonstrate that IL-17 is an important cytokine not only in the early neutrophil-mediated inflammatory response, but also in T cell-mediated IFN-gamma production and granuloma formation in response to pulmonary infection by Mycobacterium bovis bacille Calmette-Guerin (BCG). IL-17 expression in the BCG-infected lung was detected from the first day after infection and the expression depended on IL-23. Our observations indicated that gamma delta T cells are a primary source of IL-17. Lung-infiltrating T cells of IL-17-deficient mice produced less IFN-gamma in comparison to those from wild-type mice 4 wk after BCG infection. Impaired granuloma formation was also observed in the infected lungs of IL-17-deficient mice, which is consistent with the decreased delayed-type hypersensitivity response of the infected mice against mycobacterial Ag. These data suggest that IL-17 is an important cytokine in the induction of optimal Th1 response and protective immunity against mycobacterial infection.

関連情報を調べる

PubMed

Interleukin-17 as an effector molecule of innate and acquired immunity against infections

Goro Matsuzaki, Masayuki Umemura

MICROBIOLOGY AND IMMUNOLOGY ( BLACKWELL PUBLISHING ) 51 ( 12 ) 1139 - 1147 2007年 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

Interleukin (IL)-17 is a proinflammatory cytokine which induces differentiation and migration of neutrophils through induction of cytokines and chemokines including granulocyte-colony stimulating factor and CXCL8/IL-8. IL-17-producing CD4(+) T cells (Th17) have pivotal role in pathogenesis of autoimmune diseases. IL-17 is also involved in protective immunity against various infections. IL-17 has important role in induction of neutrophil-mediated protective immune response against extracellular bacterial or fungal pathogens such as Klebsiella pneumoniae and Candida albicans. Importance of IL-17 in protection against intracellular pathogens including Mycobacterium has also been reported. Interestingly, not only CD4(+) T cells but atypical CD4(-)CD8(-) T cells expressing T cell receptor (TCR) gamma delta produce IL-17, and IL-17 producing cells participate in both innate and acquired immune response to infections. Furthermore, neutrophil induction may not be the only mechanism of IL-17-mediated protective immunity. IL-17 seems to participate in host defense through regulation of cell-mediated immunity or induction of antimicrobial peptides such as beta-defensins. In this review, we summarize recent progress on the role of IL-17 in immune response against infections, and discuss possible application of IL-17 in prevention and treatment of infectious diseases.

関連情報を調べる

PubMed

Suppression of the bacterial antigen-specific T cell response and the dendritic cell migration to the lymph nodes by osteopontin.

Begum MD, Umemura M, Kon S, Yahagi A, Hamada S, Oshiro K, Gotoh K, Nishizono A, Uede T, Matsuzaki G

Microbiology and immunology ( Wiley ) 51 ( 1 ) 135 - 47 2007年

掲載種別: 研究論文（学術雑誌）

Osteopontin (OPN) has been reported to enhance the interferon (IFN)-gamma-producing Th1-type T cell response through the induction of interleukin (IL)-12 and the suppression of IL-10. We therefore investigated whether OPN could enhance Th1 induction by vaccination against bacterial antigen in vivo. Unexpectedly, the co-inoculation of OPN suppressed the induction of IFN-gamma-producing CD4(+) T cells and T cell proliferative response after the subcutaneous heat-killed Listeria monocytogenes (HKLM) immunization. These results suggest that OPN down-regulates T cell priming. Since dendritic cells (DC) play a pivotal role in T cell priming, we next analyzed the effects of OPN on DC. The addition of OPN into the culture of either bone marrow-derived immature DC or an immature DC line JAWSII showed no effects on the expression of MHC class II, CD80, and CD86 molecules before and after HKLM stimulation. Consistently, in vitro OPN-treated DC showed a normal antigen-presenting function to an established Listeria-specific Th1-type T cells. However, when the DC were transferred into the footpad with HKLM and OPN, the migration of the transferred DC into the regional LN was suppressed in comparison to the DC transferred with HKLM alone. Furthermore, the addition of OPN into the culture of the DC line and HKLM severely suppressed the HKLM-induced expression of CCR7 chemokine receptor which is an important factor in the migration of DC into LN. All the results suggest the existence of an OPN-mediated negative feedback mechanism in the T cell immune response through the regulation of DC migration.

この論文にアクセスする

DOI
関連情報を調べる

PubMed CiNii Research

Suppressor of cytokine signalling 1 in lymphocytes regulates the development of intestinal inflammation in mice

Inagaki-Ohara K, Sasaki A, Matsuzaki G, Ikeda T, Hotokezaka M, Chijiiwa K, Kubo M, Yoshida H, Nawa Y, Yoshimura A

GUT ( Gut ) 55 ( 2 ) 212 - 219 2006年02月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

Background and aims: Imbalance between pro- and anti-inflammatory cytokines produced by intestinal T cells induces inflammatory bowel diseases (IBD). However, the importance of regulation of cytokine signalling in IBD has not been fully clarified. We have demonstrated that suppressor of cytokine signalling 1 (SOCS1) is expressed in inflamed tissues in an experimental colitis model. In the present study, we investigated the role of SOCS1 in colitis models to clarify the mechanism of IBD development. Methods: Intestinal T cells in transgenic mice expressing high levels of SOCS1 in lymphocytes (SOCS1Tg mice) were characterised by flow cytometric analysis and cytokine production from intestinal T cells was determined by ELISA. 2,4,6-Trinitrobenzene sulphonic acid (TNBS) induced colitis was induced in SOCS1Tg mice and severity was compared with control littermates by measurement of survival rates. Intracellular signalling was assessed by western blotting analysis. Results: SOCS1Tg mice developed colitis spontaneously with age. Young SOCS1Tg mice less than 15 weeks of age, before the onset of colitis, were susceptible to TNBS induced colitis. Intestinal T cells of SOCS1Tg mice showed increased interferon c and tumour necrosis factor a production and decreased transforming growth factor beta production. Expression of cytotoxic T lymphocyte associated antigen 4 (CTLA-4), a negative regulator of T cell activation, in SOCS1Tg mice was severely impaired at the protein level although mRNA levels of CTLA-4 in SOCS1Tg mice were comparable with those in control mice. Conclusions: Our data suggest that SOCS1 plays an important role in the regulation of colitis by controlling intestinal T cell activation mediated through CTLA-4 expression.

この論文にアクセスする

DOI
関連情報を調べる

PubMed

Fas Ligand Induces Cell-Autonomous IL-23 Production in Dendritic Cells, a Mechanism for Fas Ligand-Induced IL-17 Production

Hiroyasu Kidoya, Masayuki Umemura, Takaya Kawabe, Goro Matsuzaki, Ayano Yahagi, Ryu Imamura, Takashi Suda

The Journal of Immunology ( The American Association of Immunologists ) 175 ( 12 ) 8024 - 8031 2005年12月

掲載種別: 研究論文（学術雑誌）

<jats:title>Abstract</jats:title> <jats:p>Fas ligand (FasL) has the potential to induce inflammation accompanied by massive neutrophil infiltration. We previously reported that FasL rapidly induces the production of various inflammatory cytokines including IL-1β and IL-17. In this study, we investigated the mechanism of the FasL-induced IL-17 production. We found that the culture supernatant of mouse resident peritoneal exudate cells (PEC) cocultured with FasL-expressing tumor (FFL) cells induced IL-17 production in freshly isolated resident PEC. Anti-IL-1β Ab strongly inhibited the IL-17-inducing activity. However, rIL-1β by itself induced only weak IL-17 production. Intriguingly, anti-IL-12 Ab but not an IL-15-neutralizing agent, IL15R-Fc, strongly inhibited the FasL-induced IL-17-inducing activity. IL-23, which shares the p40 subunit with IL-12, but not IL-12 itself, induced IL-17 production synergistically with IL-1β in resident PEC. FasL induced the production of IL-23 in PEC in vivo and in vitro, and IL-17 production following the i.p. injection of FFL cells was severely impaired in p40−/− mice, indicating that IL-23 plays an important role in the FasL-induced IL-17 production. FFL also induced the production of IL-23 in bone marrow- or PEC-derived dendritic cells (DCs). Finally, FasL induced only weak p40 production in a mixture of p40−/− and Fas−/− DC, indicating that FasL induces IL-23 production in DC mainly in a cell-autonomous manner.</jats:p>

この論文にアクセスする

DOI
関連情報を調べる

CiNii Research

Fas ligand induces cell-autonomous IL-23 production in dendritic cells, a mechanism for Fas ligand-induced IL-17 production

H Kidoya, M Umemura, T Kawabe, G Matsuzaki, A Yahagi, R Imamura, T Suda

JOURNAL OF IMMUNOLOGY ( AMER ASSOC IMMUNOLOGISTS ) 175 ( 12 ) 8024 - 8031 2005年12月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

Fas ligand (FasL) has the potential to induce inflammation accompanied by massive neutrophil infiltration. We previously reported that FasL rapidly induces the production of various inflammatory cytokines including IL-1 beta and IL-17. In this study, we investigated the mechanism of the FasL-induced IL-17 production. We found that the culture supernatant of mouse resident peritoneal exudate cells (PEC) cocultured with FasL-expressing tumor (FFL) cells induced IL-17 production in freshly isolated resident PEC. Anti-IL-1 beta Ab strongly inhibited the IL-17-inducing activity. However, rIL-1 beta by itself induced only weak IL-17 production. Intriguingly, anti-IL-12 Ab but not an IL-15-neutralizing agent, IL15R-Fc, strongly inhibited the FaSL-induced IL-17-inducing activity. IL-23, which shares the p40 subunit with IL-12, but not IL-12 itself, induced IL-17 production synergistically with IL-1 beta in resident PEC. FasL induced the production of IL-23 in PEC in vivo and in vitro, and IL-17 production following the i.p. injection of FFL cells was severely impaired in p40(-/-) mice, indicating that IL-23 plays an important role ill the FasL-induced IL-17 production. FFL, also induced the production of IL-23 in bone marrow- or PEC-derived dendritic cells (DCs). Finally, FasL induced only weak p40 production in a mixture of p40(-/-) and Fas(-/-) DC, indicating that FasL induces IL-23 production in DC mainly in a cell-autonomous manner.

関連情報を調べる

PubMed

The regulatory functions of Ly-49A, Ly-49D and Ly-49G2 on NK cells in the recognition and rejection of the alloantigen in vivo

Shimizu I, Tomita Y, Iwai T, Zhang QW, Matsuzaki G, Nomoto K, Yasui H

TRANSPLANT INTERNATIONAL ( Transplant International ) 18 ( 9 ) 1090 - 1099 2005年09月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

Ly-49A is an inhibitory receptor that binds H-2D(d) and H-2D(.)(k) The downregulation of Ly-49A is thought to mediate NK self tolerance in vivo. In this study, we analyzed the regulation of Ly-49A, D and G2 on NK cells in an in vivo rejection model. After injection with 1 x 10(8) B10.D2 spleen cells (SC) into B 10 mice, we found Ly-49A downregulated within 3 h on NK cells of B10 mice, whereas expressions of Ly-49D and G2 were augmented. To investigate effects of different expression patterns of Ly-49 receptors on NK cells, Ly-49A, D or G2-depleted B10 mice were inoculated with B10.D2 SC. NK cells from SC of Ly-49A-depleted and B10.D2 SC-injected B10 mice showed enhanced cytotoxicity to D-d-positive targets in vitro. Furthermore, reduced numbers of B10.D2 SC were observed in Ly-49A or G2-depleted B10 mice, whereas increased numbers of B10.D2 SC were observed in Ly-49D-depleted B10 mice after inoculation with B10.D2 SC in vivo. These findings indicated that the downregulation of Ly-49A and the augmentation of Ly-49D expression may mediate NK cells to recognize and kill D-d antigen efficiently. In conclusion, each Ly-49 isoform may play independent roles in the regulation of activation or inhibition on NK cells.

この論文にアクセスする

DOI
関連情報を調べる

PubMed

Intraepithelial lymphocytes express junctional molecules in murine small intestine

Inagaki-Ohara K.

Biochemical and Biophysical Research Communications ( Biochemical and Biophysical Research Communications ) 331 ( 4 ) 977 - 983 2005年06月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

Intestinal intraepithelial lymphocytes (IEL) that reside at basolateral site regulate the proliferation and differentiation of epithelial cells (EC) for providing a first line of host defense in intestine. However, it remains unknown how IEL interact and communicate with EC. Here, we show that IEL express junctional molecules like EC. We identified mRNA expression of the functional molecules in IEL such as zonula occludens (ZO)-1, occludin and junctional adhesion molecule (JAM) (tight junction), beta-catenin and E-cadherin (adherens junction), and connexin26 (gap junction). IEL constitutively expressed occludin and E-cadherin at protein level, while other T cells in the thymus, spleen, liver, mesenteric lymph node, and Peyer's patches did not. gamma delta IEL showed higher level of these expressions than alpha beta IEL. The expression of occludin was augmented by anti-CD3 Ab stimulation. These results suggest the possibility of a novel role of IEL concerning epithelial barrier and communication between IEL and EC. (c) 2005 Elsevier Inc. All rights reserved.

この論文にアクセスする

DOI
関連情報を調べる

PubMed

Absent mRNA Accumulation of Th1 or Th2 Cytokines in Heart Allografts with Chimerism-Based Drug-Induced Tolerance

TOMITA YUKIHIRO, ZHANG QI-WEI, MATSUZAKI GORO, SHIMIZU ICHIRO, IWAI TOSHIRO, OKANO SHINJI, NOMOTO KIKUO, YASUI HISATAKA

Surgery today : the Japanese journal of surgery 35 ( 5 ) 364 - 370 2005年05月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

関連情報を調べる

CiNii Research

Absent mRNA accumulation of Th1 or Th2 cytokines in heart allografts with chimerism-based drug-induced tolerance

Tomita Y, Zhang QW, Matsuzaki G, Shimizu I, Iwai T, Okano S, Nomoto K, Yasui H

SURGERY TODAY ( Surgery Today ) 35 ( 5 ) 364 - 370 2005年05月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

Purpose. We recently described using cyclophosphamide (CP) plus busulfan (BU) to create drug-induced skin and heart allograft tolerance capable of regularly overcoming fully H-2 mismatched barriers in mice. The present study investigates the intragraft mRNA expressions of Th1 and Th2 cytokines. Methods. This method consists of the intravenous (i.v.) injection of 1 x 10(8) allogeneic spleen cells on day 0, the intraperitoneal injection of 200 mg/ kg CP and 30 mg/ kg BU on day 2, and the i.v. injection of 1 x 10(7) T cell-depleted allogeneic bone marrow cells from the same strain of mice on day 3. Heart grafting (HG) was performed on day 28. Chimerism in the peripheral blood was monitored by flow cytometric (FCM) analysis. The frequency of certain Vβ families was determined by FCM to assess deletion of donor-reactive T cells. Th1 ( interleukin [IL]-2, interferon [IFN]-γ) and Th2 (IL-4, IL-10) cytokine expression in the heart grafts was analyzed with reverse transcription - polymerase chain reaction. Results. In a fully MHC mismatched combination of B10. D2 (H-2(d), IE+) --> B10 (H-2(b), IE-), B10. D2 heart grafts were accepted permanently in a donor-specific manner, mixed chimerism was observed, and IE-reactive Vβ 11(+) T cells were specifically reduced in the periphery from the recipient B10 mice. In the donor B10. D2 heart grafts, there was no accumulation of Th1 (IL-2, IFN-γ) or Th2 (IL-4, IL-10) cytokines. Conclusions. These results show that the drug-induced tolerance we established can regularly induce long-lasting heart allograft tolerance without intragraft mRNA accumulation of Th1 or Th2.

この論文にアクセスする

DOI
関連情報を調べる

PubMed

Anti-tumour activity of heat-shock protein 60-recognizing CD4(+) T cells against syngeneic murine renal cell carcinoma

Eto M, Harada M, Tatsugami K, Harano M, Koga H, Matsuzaki G, Naito S

BJU INTERNATIONAL ( BJU International ) 95 ( 3 ) 420 - 423 2005年02月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

To determine whether heat-shock protein (HSP) 60-recognizing CD4(+) T cells show antitumour activity against renal carcinoma (RENCA) cells, as HSP is highly expressed by tumour cells and induced in cells by various stresses, including transformation. RENCA, a renal cortical adenocarcinoma cell line of BALB/c origin, was used. Expression of major histocompatibility complex (MHC) class I, class II and HSP-60 on RENCA tumour cells was analysed by flow cytometry. BASL1.1, an autoreactive T-helper type 1 type CD4(+) T cell clone established by us, and that recognises HSP-60, was also used for a tumour-neutralising assay. The RENCA cells were negative for MHC class II, but expressed intracellular HSP-60. In the tumour-neutralising assay, BASL1.1 cells significantly suppressed the in vivo growth of RENCA cells. Three of five mice rejected RENCA cells when co-inoculated with BASL1.1 cells. These results indicate that HSP-60-recognizing CD4(+) T cells have the potential to eliminate renal cell carcinoma in vivo and that the eliciting of an anti-self T cell response at the tumour site can lead to regression of renal cancer.

この論文にアクセスする

DOI
関連情報を調べる

PubMed

Vdelta1+ gammadelta T cells producing CC chemokines may bridge a gap between neutrophils and macrophages in innate immunity during Escherichia coli infection in mice.

Tagawa T, Nishimura H, Yajima T, Hara H, Kishihara K, Matsuzaki G, Yoshino I, Maehara Y, Yoshikai Y

Journal of immunology (Baltimore, Md. : 1950) ( The American Association of Immunologists ) 173 ( 8 ) 5156 - 64 2004年10月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

<jats:title>Abstract</jats:title> <jats:p>An influx of neutrophils followed a short time later by an influx of macrophages to the infected site plays a key role in innate immunity against Escherichia coli infection. We found in this study that Vδ1−/− mice exhibited impaired accumulation of peritoneal macrophages but not neutrophils and delayed bacterial clearance after i.p. inoculation with E. coli. Peritoneal γδ T cells from E. coli-infected wild-type mice produced CCL3/MIP-1α and CCL5/RANTES in response to γδ TCR triggering in vitro, whereas such production was not evident in γδ T cells from E. coli-infected Vδ1−/− mice. Neutralization of CCL3/MIP-1α by a specific mAb in vivo significantly inhibited the accumulation of macrophages in the peritoneal cavity after E. coli infection, resulting in exacerbated bacterial growth in the peritoneal cavity. These results suggest that Vδ1+ γδ T cells bridge a gap between neutrophils and macrophages in innate immunity during E. coli infection mediated by production of CC chemokines, enhancing macrophage trafficking to the site of infection.</jats:p>

この論文にアクセスする

DOI
関連情報を調べる

PubMed CiNii Research

V delta 1(+) gamma delta T cells producing CC chemokines may bridge a gap between neutrophils and macrophages in innate immunity during Escherichia coli infection in mice

T Tagawa, H Nishimura, T Yajima, H Hara, K Kishihara, G Matsuzaki, Yoshino, I, Y Maehara, Y Yoshikai

JOURNAL OF IMMUNOLOGY ( AMER ASSOC IMMUNOLOGISTS ) 173 ( 8 ) 5156 - 5164 2004年10月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

An influx of neutrophils followed a short time later by an influx of macrophages to the infected site plays a key role in innate immunity against Escherichia coli infection. We found in this study that Vdelta1(-/-) mice exhibited impaired accumulation of peritoneal macrophages but not neutrophils and delayed bacterial clearance after i.p. inoculation with E. coli. Peritoneal gammadelta T cells from E. coli-infected wild-type mice produced CCL3/MIP-1alpha and CCL5/RANTES in response to gammadelta TCR triggering in vitro, whereas such production was not evident in gammadelta T cells from E. coli-infected Vdelta1(-/-) mice. Neutralization of CCL3/MIP-1alpha by a specific mAb in vivo significantly inhibited the accumulation of macrophages in the peritoneal cavity after E. coli infection, resulting in exacerbated bacterial growth in the peritoneal cavity. These results suggest that Vdelta1(+) gammadelta T cells bridge a gap between neutrophils and macrophages in innate immunity during E. coli infection mediated by production of CC chemokines, enhancing macrophage tracking to the site of infection.

関連情報を調べる

PubMed

Involvement of IL-17 in Fas ligand-induced inflammation

UMEMURA Masayuki, KAWABE Takaya, SHUDO Koyo, KIDOYA Hiroyasu, FUKUI Masayuki, ASANO Masahide, IWAKURA Yoichiro, MATSUZAKI Goro, IMAMURA Ryu, SUDA Takashi

International immunology 16 ( 8 ) 1099 - 1108 2004年08月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

関連情報を調べる

CiNii Research

Involvement of IL-17 in Fas ligand-induced inflammation

Umemura M.

International Immunology ( International Immunology ) 16 ( 8 ) 1099 - 1108 2004年08月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

Fas ligand (FasL) has been well characterized as a death factor. However, recent studies revealed that ectopic expression of FasL induces inflammation associated with massive neutrophil infiltration. We previously demonstrated that the neutrophil infiltration-inducing activity of FasL is partly dependent on, but partly independent of, IL-1beta. Here we investigated the cytokine profile of peritoneal lavage fluid obtained from mice that received i.p. injections of FFL, a FasL-expressing tumor cell line. We found that FFL injection caused a marked increase of not only IL-1beta but also IL-6, IL-17, IL-18, KC/chemokine CXC ligand 1 and macrophage inflammatory protein (MIP)-2, but not of IL-1alpha, IFN-gamma, TGF-beta or TNF-alpha. The FFL-induced cytokine production was not observed in Fas-deficient Ipr mice. Among cells transfected to express individually IL-1beta, IL-6, IL-17, or IL-18, only those expressing IL-1beta and IL-17 induced neutrophil infiltration. In these analyses, as little as 20 pg of peritoneal IL-17 induced neutrophil infiltration. The peritoneal IL-17 levels after FFL-injection were greatly diminished in IL-1-deficient mice. However, the IL-17 level was still above the threshold for neutrophil infiltration. Consistent with this, co-administration of the anti-IL-17 antibody with FFL diminished the peritoneal KC levels and neutrophil infiltration in IL-1-deficient mice. In addition, the expression of IL-17 by the tumor cells inhibited tumor growth in wild-type and nude mice. These results indicate that FasL is an upstream inflammatory factor that induces a variety of other inflammatory cytokines in vivo, and suggest that IL-17 is involved in FasL-induced inflammation in the absence of IL-1beta.

この論文にアクセスする

DOI
関連情報を調べる

PubMed

Mucosal T Cells Bearing TCRγδ Play a Protective Role in Intestinal Inflammation

Kyoko Inagaki-Ohara, Takatoshi Chinen, Goro Matsuzaki, Atsuo Sasaki, Yukiko Sakamoto, Kenji Hiromatsu, Fukumi Nakamura-Uchiyama, Yukifumi Nawa, Akihiko Yoshimura

The Journal of Immunology ( The American Association of Immunologists ) 173 ( 2 ) 1390 - 1398 2004年07月

掲載種別: 研究論文（学術雑誌）

<jats:title>Abstract</jats:title> <jats:p>Intestinal intraepithelial lymphocytes (IEL) bearing TCRγδ represent a major T cell population in the murine intestine. However, the role of γδ IEL in inflammatory bowel diseases (IBD) remains controversial. In this study, we show that γδ IEL is an important protective T cell population against IBD. γδ T cell-deficient (Cδ−/−) mice developed spontaneous colitis with age and showed high susceptibility to Th1-type 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis at a young age. Transfer of γδ IEL to Cδ−/− mice ameliorated TNBS-induced colitis, which correlated with decrease of IFN-γ and TNF-α production and an increase of TGF-β production by IEL. Furthermore, a high level of IL-15, which inhibits activation-induced cell death to terminate inflammation, was expressed more in intestinal epithelial cells (EC) from TNBS-treated Cδ−/− mice than in those from wild-type mice. EC from wild-type mice significantly suppressed the IFN-γ production of IEL from TNBS-treated Cδ−/− mice, whereas EC from TNBS-treated Cδ−/− mice did not. These data indicate that γδ IEL play important roles in controlling IBD by regulating mucosal T cell activation cooperated with EC function. Our study suggests that enhancement of regulatory γδ T cell activity is a possible new cell therapy for colitis.</jats:p>

この論文にアクセスする

DOI
関連情報を調べる

CiNii Research

Mucosal T cells bearing TCR gamma delta play a protective role in intestinal inflammation

K Inagaki-Ohara, T Chinen, G Matsuzaki, A Sasaki, Y Sakamoto, K Hiromatsu, F Nakamura-Uchiyama, Y Nawa, A Yoshimura

JOURNAL OF IMMUNOLOGY ( AMER ASSOC IMMUNOLOGISTS ) 173 ( 2 ) 1390 - 1398 2004年07月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

Intestinal intraepithelial lymphocytes (IEL) bearing TCRgammadelta represent a major T cell population in the murine intestine. However, the role of gammadelta IEL in inflammatory bowel diseases (IBD) remains controversial. In this study, we show that gammadelta IEL is an important protective T cell population against IBD. gammadelta T cell-deficient (CS-/-) mice developed spontaneous colitis with age and showed high susceptibility to Th1-type 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis at a young age. Transfer of gammadelta IEL to Cdelta(-/-) mice ameliorated TNBS-induced colitis, which correlated with decrease of IFN-gamma and TNF-alpha production and an increase of TGF-beta production by IEL. Furthermore, a high level of IL-15, which inhibits activation-induced cell death to terminate inflammation, was expressed more in intestinal epithelial cells (EC) from TNBS-treated Cdelta(-/-) mice than in those from wild-type mice. EC from wild-type mice significantly suppressed the IFN-gamma production of IEL from TNBS-treated Cdelta(-/-) mice, whereas EC from TNBS-treated Cdelta(-/-) mice did not. These data indicate that gammadelta IEL play important roles in controlling IBD by regulating mucosal T cell activation cooperated with EC function. Our study suggests that enhancement of regulatory gammadelta T cell activity is a possible new cell therapy for colitis.

Mucosal T cells bearing gamma delta T-cell receptor play a protective role in intestinal inflammation

K Inagaki-Ohara, G Matsuzaki, A Sasaki, Y Nawa, A Yoshimura

IMMUNOLOGY 2004: GENOMIC ISSUES, IMMUNE SYSTEM ACTIVATION AND ALLERGY ( MEDIMOND PUBLISHING CO ) 173 ( 2 ) 485 - 489 2004年 [ 査読有り ]

掲載種別: 研究論文（国際会議プロシーディングス）

We investigated whether gammadelta intraepithelial lymphocytes (IEL) are an important protective T-cell population against inflammatory bowel disease (IBD). gammadelta T cell-deficient (Cdelta(-/-)) mice developed spontaneous colitis with age and showed high susceptibility to Th1-type TNBS-induced colitis at a young age. Transfer of gammadelta to Cdelta(-/-) mice ameliorated TNBS-induced colitis, which correlated with decrease of IFN-gamma and TNF-alpha production and an increase of TGF-beta production by IEL. Furthermore, a higher level of IL-15 was expressed in intestinal epithelial cells (EC) from TNBS-treated Cdelta(-/-) mice than in those from WT mice. EC from WT mice significantly suppressed the TFN-gamma production of IEL from TNBS-treated Cdelta(-/-) mice, whereas EC from TNBS-treated Cdelta(-/-) mice did not. These data indicate that gd IEL play important roles in controlling IBD by regulating mucosal T-cell activation in cooperation with EC function and suggests that enhancement of regulatory 76 T-cell activity is a possible new cell-therapy for colitis.

関連情報を調べる

PubMed

Interleukin-15 as an Immune Adjuvant To Increase the Efficacy of Mycobacterium bovis Bacillus Calmette-Gue'rin Vaccination

Umemura.M, Nishimura.H, Saito.K, Yajima.T, Matsuzaki.G, Mizuno.S, Sugawara.I, Yoshikai.Y

Immune. ( その他の出版社 ) 71 ( 10 ) 6045 - 6048 2003年03月

掲載種別: 研究論文（その他学術会議資料等）

この論文にアクセスする

DOI

Interleukin-15 as an immune adjuvant to increase the efficacy of Mycobacterium bovis bacillus Calmette-Gu

Umemura, M., Nishimura, H., Saito, K., Yajima, T., Matsuzaki, G., Mizuno, S., Sugawara, I., and Yoshikai, Y

Immune. ( その他の出版社 ) 71 ( 10 ) 6045 - 6048 2003年

掲載種別: 研究論文（その他学術会議資料等）

Induction of protective immunity by primed B-1 cells in Toxoplasma gondii-infected B cell-deficient mice

M Chen, HS Mun, LX Piao, F Aosai, K Norose, RM Mohamed, US Belal, H Fang, AK Ahmed, HK Kang, G Matsuzaki, D Kitamura, A Yano

MICROBIOLOGY AND IMMUNOLOGY ( CENTER ACADEMIC PUBL JAPAN ) 47 ( 12 ) 997 - 1003 2003年 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

We examined the role of B-1 cells in protection against Toxoplasma gondii infection using B cell-deficient mice (muMT mice). We found that primed but not naive B-1 cells from wild-type C57BL/6 mice protected B cell-deficient recipients from challenge infection. All muMT mice transferred with primed B-1 cells survived more than 5 months after T gondii infection, whereas 100% of muMT mice transferred with naive B-1 cells succumbed by 18 days after infection. Additionally, high expression of both T help (Th) 1- and Th2-type cytokines and a high level of nitric oxide production were observed in T gondii-infected muMT mice transferred with primed B-1 cells. Thus, it was clearly demonstrated that B-1 cells play an important role in host protection against T. gondii infection in muMT mice.

関連情報を調べる

PubMed

Mechanism of murine Vgamma1+ gamma delta T cell-mediated innate immune response against Listeria monocytogenes infection.

Matsuzaki G, Yamada H, Kishihara K, Yoshikai Y, Nomoto K

European journal of immunology ( European Journal of Immunology ) 32 ( 4 ) 928 - 35 2002年04月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

Murine gammadelta T cells participate in innate immune response against infection of the intracellular bacterium Listeria monocytogenes. In the present report, we analyzed the mechanism of the gammadelta T cell-mediated response against L. monocytogenes infection. gammadelta T cell-enriched spleen cells of L. monocytogenes-infected mice produced IFN-gamma in vitro in response to L. monocytogenes-infected spleen cells, The IFN-gamma production was abrogated by depletion of Vgamma1(+) gammadelta T cells. IFN-gamma production of the Vy1(+) gammadelta T cells in response to L. monocytogenes-infected spleen cells required IL-12. However, addition of Fab fragment of anti-TCR gammadelta monoclonal antibodies (mAb) failed to block the response, suggesting that the response requires no TCR-mediated antigen recognition. Interestingly, Vgamma1(+) gammadelta T cells of naive mice also produced IFN-gamma in response to L. monocytogenes-infected spleen cells in an IL-12-dependent manner. Furthermore, the IL-12 receptor (IL-12R) gene was expressed on the Vgamma1(+) gammadelta T cells of naive mice as well as those of L. monocytogenes-infected mice although naive alphabeta T cells lack IL-12R expression. All the results suggest that the Vgamma1(+) gammadelta T cells participate in immune surveillance against intracellular bacterial infection through quick production of IFN-gamma in response to infection-induced IL-12 without antigen-driven clonal expansion and maturation.

この論文にアクセスする

DOI
関連情報を調べる

PubMed

Mechanism of murine Vg1+ gd T cell-mediated innate immune response against Listeria monocytogenes infection.

Matsuzaki.G, Yamada.H, Kishihara.K, Yoshikai.Y, Nomoto.K

Eur. J. Immunol. ( その他の出版社 ) 32 ( 4 ) 928 - 935 2002年03月

掲載種別: 研究論文（その他学術会議資料等）

Heart allograft tolerance without development of posttransplant cardiac allograft vasculopathy in chimerism-based, drug-induced tolerance.

Zhang.Q.W, Tomita.Y, Matsuzaki.G, Shimizu.I, Iwai.T, Okano.S, Minagawa.R, Nakashima.Y, Sueishi.K, Nomoto.K, Nomoto.K

Transplantation ( その他の出版社 ) 73 ( 4 ) 625 - 626 2002年03月

掲載種別: 研究論文（その他学術会議資料等）

この論文にアクセスする

DOI

Mechanism of murine Vg1+ gd T cell-mediated innate immune response against Listeria monocytogenes infection.

Matsuzaki, G., Yamada, H., Kishihara, K., Yoshikai, Y., and Nomoto, K.

Eur. J. Immunol. ( その他の出版社 ) 32 ( 4 ) 928 - 935 2002年

掲載種別: 研究論文（その他学術会議資料等）

Heart allograft tolerance without development of posttransplant cardiac allograft vasculopathy in chimerism-based, drug-induced tolerance.

Zhang, Q. W., Tomita, Y., Matsuzaki, G., Shimizu, I., Iwai, T., Okano, S., Minagawa, R., Nakashima, Y., Sueishi, K., Nomoto, K., and Nomoto, K.

Transplantation ( その他の出版社 ) 73 ( 4 ) 625 - 626 2002年

掲載種別: 研究論文（その他学術会議資料等）

Different expressions of Ly-49 receptors on mouse NK and NK T cells.

Shimizu I, Tomita Y, Zhang QW, Iwai T, Matsuzaki G, Yasui H

Immunobiology ( Immunobiology ) 204 ( 4 ) 466 - 76 2001年12月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

NK T cells are a unique T cell lineage and are reported to express Ly-49 molecules which are inhibitory receptors specific for class I molecules. In this study, we examined the expression of activation and inhibitory receptors on NK T cells in different organs of beta2-microgloblin knock out (beta 2mKO), C57BL/6 (B6; H-2(b)), C57BL/10 (B10; H-2(b)) and B10.D2 (H-2(d)) mice. The low level expression of inhibitory receptors Ly-49A and G2 on NK T cells as well as NK cells, which are specific for D-d antigen, were observed in B10.D2 mice, but not in beta 2mKO, B6, or B10 mice. The small percentage of inhibitory receptor Ly-49C positive NK and NKT cells, which is specific for K-b and D-d antigens, was observed in BMC, LMC and SC of B6, B10 and B10.D2 mice compared to beta 2mKO mice. On the contrary, the large percentage of Ly-49C positive NK T cells was observed in thymocytes of B6, B10 and B10.D2 mice compared to beta 2mKO mice. Interestingly, Ly-49D activation receptor was hardly detectable on NK T cells in any organs of the 4 strains of mice whereas it was clearly detectable on NK cells. These findings suggest that the unique characteristics of NK T cells may mediate regulatory function in MHC class I antigen-restricted immunity.

この論文にアクセスする

DOI
関連情報を調べる

PubMed

Reevaluation of the origin of CD44(high) "memory phenotype" CD8 T cells: comparison between memory CD8 T cells and thymus-independent CD8 T cells

H Yamada, G Matsuzaki, QJ Chen, Y Iwamoto, K Nomoto

EUROPEAN JOURNAL OF IMMUNOLOGY ( WILEY-V C H VERLAG GMBH ) 31 ( 6 ) 1917 - 1926 2001年06月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

CD44(high)CD8 T cells in naive mice, which increase with age, and are often referred to as memory CD8 T cells. However, since thymus-independent CD8 T cells have also been shown to be CD44(high), the origin of the CD44(high)CD8 T cells in naive mice remains unclear. In this study, we compared the characteristics of memory CD8 T cells and thymus-independent CD8 T cells in TCR transgenic mice to clarify the origin of the CD44(high)CD8 T cells in naive normal mice. The memory and thymus-independent CD8 T cells showed differences in surface molecules, spontaneous cell death, cytokine production, and response to IL-2R binding of cytokines. Importantly, the "memory phenotype" CD8 T cells in naive normal mice showed similar characteristics to the thymus-independent CD8 T cells, but differed greatly from "true" memory CD8 T cells in the TCR transgenic mice. Therefore, we conclude that a significant part of the CD44(high) memory phenotype CD8 T cells in naive normal mice represents thymus-independent CD8 T cells, which may participate in age-related changes in immune responses.

この論文にアクセスする

DOI
関連情報を調べる

PubMed

Chronic rejection in H-2 matched cardiac allografts: early emergence of vasculopathy, alloantibody, and accumulation of IFN-gamma and IL-10 mRNA.

Zhang QW, Tomita Y, Matsuzaki G, Uchida T, Yoshikawa M, Nakashima Y, Sueishi K, Nomoto K, Yasui H

Transplant international : official journal of the European Society for Organ Transplantation ( Transplant International ) 14 ( 3 ) 143 - 52 2001年06月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

Cardiac allograft vasculopathy (CAV) is one of the crucial problems of clinical heart transplantation. We have developed a novel model of murine cardiac allograft rejection, in which chronic rejection associated with CAV occurs in its natural course. In this study we analyzed the pathogenesis of chronic cardiac allograft rejection using an H-2 matched multiple minor histocompatibility antigen-mismatched combination, AKR (H-2(k)) to C3H (H-2(k)) recipient mice. All the cardiac allografts survived for more than 100 days but were rejected within 260 days post-transplant (n = 13; mean survival times +/- standard deviation = 189.0 +/- 72.0; median = 210). The heartbeats of the graft became gradually weaker throughout the duration of the rejection process. Serial histological analyses with hematoxylin and eosin, elastica van Gieson or Masson trichrome staining revealed mononuclear cell infiltration and intimal thickening (i.e. CAV) which started in most grafts at 2 weeks post-transplant. These pathological changes eventually developed to severe graft fibrosis, and the severity of these changes correlated with the deterioration of the heartbeats. Production of anti-donor antibodies in most recipients was detectable by 2 weeks post-transplant, it peaked before day 100, and subsided before rejection was complete in most grafts. Intragraft expression of IFN-gamma and IL-10 mRNA was demonstrated by reverse transcriptase-polymerase chain reaction during early periods post-transplant. In this study, we demonstrate a novel model feasible for analysis of chronic cardiac allograft rejection, in which the vascular rejection processes, including fibrosis and alloantibody production, can be tested from an early stage on, after transplantation.

この論文にアクセスする

DOI
関連情報を調べる

PubMed

Reevaluation of the origin of CD44high "memory phenotype" CD8 T cells: comparison between memory CD8 T cells and thymus-independent CD8 T cells

Yamada.H, Matsuzaki.G, Chen.Q.J, Iwamoto.Y, Nomoto.K

Eur. J. Immunol. ( その他の出版社 ) 31 ( 6 ) 1917 - 1926 2001年03月

掲載種別: 研究論文（その他学術会議資料等）

この論文にアクセスする

DOI

Successful priming and tolerization of T cells to orally administered antigens in B-cell-deficient mice.

Hashimoto.A, Yamada.H, Matsuzaki.G, Nomoto.K

Cell. Immunol. ( その他の出版社 ) 207 ( 1 ) 36 - 40 2001年01月

掲載種別: 研究論文（その他学術会議資料等）

この論文にアクセスする

DOI

Reevaluation of the origin of CD44high

Yamada H., Matsuzaki, G., Chen, Q. J., Iwamoto, Y. and Nomoto, K.

Eur. J. Immunol. ( その他の出版社 ) 31 ( 6 ) 1917 - 1926 2001年

掲載種別: 研究論文（その他学術会議資料等）

Successful priming and tolerization of T cells to orally administered antigens in B-cell-deficient mice.

Hashimoto, A., Yamada, H., Matsuzaki, G., and Nomoto, K.

Cell. Immunol. ( その他の出版社 ) 207 ( 1 ) 36 - 40 2001年

掲載種別: 研究論文（その他学術会議資料等）

Development of dendritic epidermal T cells with a skewed diversity of gamma delta TCRs in V delta 1-deficient mice.

Hara H, Kishihara K, Matsuzaki G, Takimoto H, Tsukiyama T, Tigelaar RE, Nomoto K

Journal of immunology (Baltimore, Md. : 1950) ( The American Association of Immunologists ) 165 ( 7 ) 3695 - 705 2000年10月

掲載種別: 研究論文（学術雑誌）

<jats:title>Abstract</jats:title> <jats:p>One of the most intriguing features of γδ T cells that reside in murine epithelia is the association of a specific Vγ/Vδ usage with each epithelial tissue. Dendritic epidermal T cells (DETCs) in the murine epidermis, are predominantly derived from the “first wave” Vγ5+ fetal thymocytes and overwhelmingly express the canonical Vγ5/Vδ1-TCRs lacking junctional diversity. Targeted disruption of the Vδ1 gene resulted in a markedly impaired development of Vγ5+ fetal thymocytes as precursors of DETCs; however, γδTCR+ DETCs with a typical dendritic morphology were observed in Vδ1−/− mice and their cell densities in the epidermis were slightly lower than those in Vδ1+/− epidermis. Moreover, the Vδ1-deficient DETCs were functionally competent in their ability to up-regulate cytokines and keratinocyte growth factor-expression in response to keratinocytes. Vγ5+ DETCs were predominant in the Vδ1−/− epidermis, though Vγ5− γδTCR+ DETCs were also detected. The Vγ5+ DETCs showed a typical dendritic shape, γδTCRhigh, and age-associated expansion in epidermis as observed in conventional DETCs of normal mice, whereas the Vγ5− γδTCR+ DETCs showed a less dendritic shape, γδTCRlow, and no expansion in the epidermis, consistent with their immaturity. These results suggest that optimal DETC development does not require a particular Vγ/Vδ-chain usage but requires expression of a limited diversity of γδTCRs, which allow DETC precursors to mature and expand within the epidermal microenvironment.</jats:p>

この論文にアクセスする

DOI
関連情報を調べる

PubMed CiNii Research

Development of dendritic epidermal T cells with a skewed diversity of gamma delta TCRs in V delta 1-deficient mice

H Hara, K Kishihara, G Matsuzaki, H Takimoto, T Tsukiyama, RE Tigelaar, K Nomoto

JOURNAL OF IMMUNOLOGY ( AMER ASSOC IMMUNOLOGISTS ) 165 ( 7 ) 3695 - 3705 2000年10月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

One of the most intriguing features of gamma delta T cells that reside in murine epithelia is the association of a specific V gamma/V delta usage with each epithelial tissue. Dendritic epidermal T cells (DETCs) in the murine epidermis, are predominantly derived from the "first wave" V gamma 5(+) fetal thymocytes and overwhelmingly express the canonical V gamma 5/V delta 1-TCRs lacking junctional diversity, Targeted disruption of the V delta 1 gene resulted in a markedly impaired development of V gamma 5(+) fetal thymocytes as precursors of DETCs; however, gamma delta TCR+ DETCs with a typical dendritic morphology were observed in V delta 1(-/-) mice and their cell densities in the epidermis were slightly lower than those in V delta 1(+/-) epidermis, Moreover, the V delta 1-deficient DETCs were functionally competent in their ability to up-regulate cytokines and keratinocyte growth factor-expression in response to keratinocytes, V gamma 5(+) DETCs were predominant in the V delta 1(-/-) epidermis, though V gamma 5(-) gamma delta TCR+ DETCs were also detected, The V gamma 5(+) DETCs showed a typical dendritic shape, gamma delta TCRhigh, and age-associated expansion in epidermis as observed in conventional DETCs of normal mid, whereas the V gamma 5(-) gamma delta TCR+ DETCs showed a less dendritic shape, gamma delta TCRlow, and no expansion in the epidermis, consistent with their immaturity. These results suggest that optimal DETC development does not require a particular V gamma/V delta-chain usage but requires expression of a limited diversity of gamma delta TCRs, which allow DETC precursors to mature and expand within the epidermal microenvironment.

関連情報を調べる

PubMed

Development of dendritic epidermal T cells with a skewed diversity of gamma delta TCRs in V delta 1-deficient mice

H Hara, K Kishihara, G Matsuzaki, H Takimoto, T Tsukiyama, RE Tigelaar, K Nomoto

JOURNAL OF IMMUNOLOGY ( AMER ASSOC IMMUNOLOGISTS ) 165 ( 7 ) 3695 - 3705 2000年10月

掲載種別: 研究論文（学術雑誌）

Characterization of CD4- CD8- CD3+ T-cell receptor-alphabeta+ T cells in murine cytomegalovirus infection.

Hossain MS, Takimoto H, Ninomiya T, Yoshida H, Kishihara K, Matsuzaki G, Kimura G, Nomoto K

Immunology ( Immunology ) 101 ( 1 ) 19 - 29 2000年09月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

In this study, we have investigated that after the intraperitoneal infection with murine cytomegalovirus (MCMV), the CD3(+) CD4(-) CD8(-)(double negative; DN) T-cell receptor (TCR)alpha beta(+) T cells increased in peritoneal cavity, liver and spleen in both resistant C57BL/6 and susceptible BALB/c mice. The total cellular population of these cells showed peak levels around day 5 after infection in all the three investigated organs and the following phenotypical and functional characteristics emerged. The peritoneal DN TCR alpha beta(+) T cells expressed highly skewed TCRV beta 8 on day 5 after infection compared with the uninfected mice, but those in spleen and liver showed moderate and low skewed TCRV beta 8, respectively. The percentages of NK1.1(+) DN TCR alpha beta(+) T cells gradually decreased as did modulation of some of their activation markers consistent with an activated cell phenotype. The peritoneal DN TCR alpha beta(+) T cells on day 5 after infection expressed the genes of interferon-gamma (IFN-gamma), tumour necrosis factor-alpha, Eta-1 (early T-cell activation-1) and MCP-1 (monocyte chemoattractant protein 1) but lacked expression of interleukin-4 (IL-4). After in vitro stimulation with phorbol 12-myristate 13-acetate and calcium ionophore in the presence of Brefeldin A, higher frequencies of intracellular IFN-gamma(+) DN TCR alpha beta(+) T cells were detected in all three investigated organs of infected mice compared with those of uninfected mice. Stimulation of peritoneal DN TCR alpha beta(+) T cells with plate-bound anti-TCR beta monoclonal antibodies showed proliferation and also produced IFN-gamma but not IL-4. These results suggest that DN TCR alpha beta(+) T cells were activated and may have an antiviral effect through producing IFN-gamma and some macrophage-activating factors during an early phase of MCMV infection.

この論文にアクセスする

DOI
関連情報を調べる

PubMed J-GLOBAL

N-3 polyunsaturated fatty acids accentuate B16 melanoma growth and metastasis through suppression of tumoricidal function of T cells and macrophages

ML Salem, K Kishihara, K Abe, G Matsuzaki, K Nomoto

ANTICANCER RESEARCH ( INT INST ANTICANCER RESEARCH ) 20 ( 5A ) 3195 - 3203 2000年09月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

Background. The antitumor effects of the n-3 polyunsaturated fatty acids (PUFAs) are still controversial and as yet undefined Materials and Methods: EPA-28, a fish oil enriched with n-3 PUFAs including eicosapentaenoic and docosahexaenoic acids, was administered subcutaneously into C57BL/6 mice before and after subcutaneous inoculation of B16 melanoma cells. The effects of EPA-28 on the antitumor activities of T cells and macrophages were investigated. Results. The treatment of the mice with EPA-28 before and after the tumor inoculation enhanced the growth and metastasis of B16 melanoma and dea eased the survival rate of the tumor-bearing mice. The treatment also decreased the number of CD4+ T cells in the spleen and tumor draining lymph nodes on day 14 after the tumor inoculation Moreover, EPA-28 suppressed the antimelanoma cytolytic activity of T cells and macrophages of the tumor bearing mice. Conclusion. The results suggest that EPA-28 treatment increased both the growth and metastasis of B16 melanoma cells by suppressing the cytolytic function of both T cells and macrophages.

関連情報を調べる

PubMed

Mixed chimerism, heart, and skin allograft tolerance in cyclophosphamide-induced tolerance

QW Zhang, Y Tomita, G Matsuzaki, M Yoshikawa, Shimizu, I, Y Nakashima, K Sueishi, K Nomoto, H Yasui

TRANSPLANTATION ( LIPPINCOTT WILLIAMS & WILKINS ) 70 ( 6 ) 906 - 916 2000年09月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

We elucidated the possible role of chimerism in skin and heart allograft tolerance using cyclophosphamide (CP)-induced tolerance. When C3H (H-2(k); Thy1.2, Mls-1(b)) mice were i.v. primed with 1x10(8) spleen cells (SC) from H-2 matched AKR (H-2(k); Thy1.1 Mls-1(a)) mice and then treated i.p. with 200 mg/kg of CP, the survivals of both AKR skin grafts and heart grafts (HG) were permanently prolonged in a tolerogen-specific fashion. After this treatment, a minimal degree of mixed chimerism, the clonal destruction of Mls-1(a)-reactive CD4(+)V beta 6(+) T cells in the periphery, and the clonal deletion of V beta 6(+) thymocytes were all observed. When AKR SC and 100 mg/kg CP were used for conditioning, the AKR HG were permanently accepted, but the survival of the AKR skin grafts was only mildly prolonged. The clonal destruction of CD4(+)V beta 6(+) T cells in the periphery and the intrathymic clonal deletion of V beta 6(+) thymocytes were induced in both the SC and the 100 mg/kg CP-treated C3H mice. A minimal degree of mixed chimerism was detectable at 4 and 12 weeks after AKR SC and 100 mg/kg CP treatment, and still did not disappear at 40 weeks, The degree of mixed chimerism induced with SC and 100 mg/kg CP was significantly lower than that with SC and 200 mg/kg CP during the observation. No posttransplant cardiac allograft vasculopathy (CAV) was observed to develop, while both the Th1 type (interferon-gamma) and Th2 type (interleukin-4 and -10) cytokine expressions decreased in the AKR HG of the tolerant C3H mice treated with both AKR SC plus 200 mg/kg CP, and AKR SC pins 100 mg/kg CP, A second set of skin grafts from donor AKR mice survived for more than 100 days in a tolerogen-specific fashion in all C3H mice treated with AKR SC and 200 mg/kg CP and also accepted the ABR HG for over 200 days, while 80% of the C3H mice treated with AKR SC and 100 mg/kg CP and accepted the AKR HG; for more than 200 days. These results strongly suggested the following conclusions: 1) the degree of chimerism can strongly influence the induction of skin and heart allograft tolerance, 2) posttransplant CAV does not develop in the donor HC; maintained by chimerism-based CP-induced tolerance, 3) the mRNA expression of both Th1 and Th2 type cytokine decreased in the donor HG maintained by chimerism-based CP-induced tolerance, and 4) the induction of skin allograft tolerance is more difficult than the prevention of posttransplant CAV.

関連情報を調べる

PubMed

Unusual cytotoxic activities of thymus-independent, self-antigen-specific CD8+ T cells

Yamada.H, Matsuzaki.G, Iwamoto.Y, Nomoto.K

Int. Immunol ( その他の出版社 ) 12 ( 12 ) 1677 - 1683 2000年03月

掲載種別: 研究論文（その他学術会議資料等）

この論文にアクセスする

DOI

Vg1+ gd T cells play protective roles at an early phase of MCMV infection through production of IFN-g.

Ninomiya.T, Takimoto.H, Matsuzaki.G, Hamano.S, Yoshida.H, Kimura.G, Nomoto.K

Immunology ( その他の出版社 ) 92 ( 2 ) 187 - 194 2000年03月

掲載種別: 研究論文（その他学術会議資料等）

TCR-Independent Activation of Extrathymically Developed, Self Antigen-Specific T Cells by IL-2/IL-15

Yamada.H, Nakamura.T, Matsuzaki.G, Iwamoto.Y, Nomoto.K

J. Immunol ( その他の出版社 ) 164 ( 4 ) 1746 - 1752 2000年03月

掲載種別: 研究論文（その他学術会議資料等）

Development of dendritic epidermal T cells with skewed diversity of gdTCRs in Vd1-deficient mice.

Hara.H, Kishihara.K, Matsuzaki.G, Takimoto.H, Tsukiyama.T, Tigelaar.R.E, Nomoto.K

J. Immunol ( その他の出版社 ) 165 ( 7 ) 3695 - 3705 2000年03月

掲載種別: 研究論文（その他学術会議資料等）

Characterization of CD4- CD8- CD3+ T-cell receptor ab+ T cells in mouse cytomegalovirus infection.

Hossain.M.S, Takimoto.H, Ninomiya.T, Yoshida.H, Kishihara.K, Matsuzaki.G, Kimura.G, Nomoto.K

Immunology ( その他の出版社 ) 101 ( 1 ) 19 - 29 2000年03月

掲載種別: 研究論文（その他学術会議資料等）

TCR-independent activation of extrathymically developed, self antigen-specific T cells by IL-2/IL-15

H Yamada, T Nakamura, G Matsuzaki, Y Iwamoto, K Nomoto

JOURNAL OF IMMUNOLOGY ( AMER ASSOC IMMUNOLOGISTS ) 164 ( 4 ) 1746 - 1752 2000年02月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

Naive intrathymically developed T cells, which express foreign Ag-specific TCR, do not express IL-2R. After antigenic stimulation, they express high affinity IL-2R, which enables IL-2 to be used as an autocrine growth factor. On the contrary, extrathymically developed T cells, which express self Ag-specific TCR but are unresponsive to antigenic stimulation, spontaneously express low affinity IL-2R. In this study, we compared the responses of these two subsets of T cells to IL-2R stimulation and examined the influences of TCR-mediated signaling on the responses. IL-2 or IL-15 augmented the proliferative response of Ag-stimulated, intrathymically developed T cells. On the other hand, extrathymically developed T cells proliferated in response to IL-2 or IL-15, independently of Ag stimulation. Furthermore, both IL-2 and IL-15 induced IFN-gamma production of these T cells, which is strikingly augmented by the presence of IL-12. These results revealed functional differences between intrathymically developed, foreign Ag-specific T cells and extrathymically developed, self Ag-specific T cells. The latter can be activated by some inflammatory cytokines, in an Ag-independent manner, similar to NK cells.

関連情報を調べる

PubMed

beta-estradiol suppresses T cell-mediated delayed-type hypersensitivity through suppression of antigen-presenting cell function and Th1 induction.

Salem ML, Matsuzaki G, Kishihara K, Madkour GA, Nomoto K

International archives of allergy and immunology ( International Archives of Allergy and Immunology ) 121 ( 2 ) 161 - 9 2000年02月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

Background: Although an immunomodulatory role for estrogens has long been demonstrated by experimental and clinical observations, the mechanism by which estrogens exert their effect on T cells has not been clearly defined. Methods: In this study we analyzed the effects of beta-estradiol (E2), at its contraceptive dose, on the delayed-type hypersensitivity (DTH) to purified protein derivatives (PPD) and associated immune response in female mice. Results: E2 treatment decreased PPD-specific DTH response, which coincided with a decrease in the leukocytes numbers in the draining lymph nodes (DLN) and spleen compared with control mice. E2 treatment also suppressed the in vitro PPD-specific proliferative response of DLN and spleen cells from PPD-primed mice. The analysis of production and gene expression of cytokines by DLN cells demonstrated that E2 treatment suppressed IL-2 and IFN-gamma production in response to PPD in vitro. In contrast, IL-4 and IL-10 gene expression by DLN cells of E2-treated mice, taken 24 h after in vivo restimulation of mice with PPD, was enhanced. Furthermore, we found that spleen APC from E2-treated mice failed to induce optimum proliferation of the PPD-primed T cells ire response to PPD in vitro. The impaired APC function by E2 was not due to induction of suppressor cell activity because addition of the normal spleen APC to APC from E2-treated mice restored the proliferative response of the PPD-primed T cells in response to PPD. Conclusion: Our results suggest that the E2-mediated inhibition of DTH reaction is due to a combination of the down regulation of APC function and deviation of the immune response from Th1-type to Th2-type. Copyright (C) 2000 S. Karger AG. Basel.

この論文にアクセスする

DOI
関連情報を調べる

PubMed

Vgamma1+ gammadelta T cells play protective roles at an early phase of murine cytomegalovirus infection through production of interferon-gamma.

Ninomiya T, Takimoto H, Matsuzaki G, Hamano S, Yoshida H, Yoshikai Y, Kimura G, Nomoto K

Immunology ( Immunology ) 99 ( 2 ) 187 - 94 2000年02月 [ 査読有り ]

掲載種別: 研究論文（学術雑誌）

Cytomegalovirus (CMV) causes severe opportunistic infection in immunocompromised hosts. The importance of conventional alpha beta T cells in protection against CMV infection has been well documented. However, the role of the second T-cell population (which express the gamma delta T-cell receptor) in CMV infection is not known. In the present study, we analysed the function and protective role of gamma delta T cells in a murine cytomegalovirus (MCMV) infection model. After intraperitoneal infection with MCMV, the number of gamma delta T cells increased in the liver and peritoneal cavity from day 3, and reached a peak on day 5. The gamma delta T cells showed an activated T-cell phenotype and predominantly expressed V gamma 1, which is known to be expressed by heat-shock protein 65 (hsp 65)-specific gamma delta T cells. Analysis of cytokine expression demonstrated that the MCMV-induced gamma delta T cells expressed interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) but not interleukin-4 (IL-4), implying their participation in the cell-mediated immune response against MCMV. Depletion of gamma delta T cells by anti-T-cell receptor (TCR) gamma delta monoclonal antibody (mAb) treatment resulted in significant increase of virus titre and decrease of IFN-gamma in the liver on day 3 after MCMV infection, which further supports the importance of gamma delta T cells in early protection against infection. Finally, the MCMV-induced gamma delta T cells produced IFN-gamma in vitro in response to hsp 65. Our results suggest that gamma delta T cells participate in early protection against MCMV infection through recognition of hsp 65 and production of IFN-gamma.

この論文にアクセスする

DOI
関連情報を調べる

PubMed J-GLOBAL

Unusual cytotoxicities of thymus-independent, self-antigen-specific CD8+ T cells.

Yamada, H., Matsuzaki, G., Iwamoto, Y., and Nomoto, K.

Int. Immunol. ( その他の出版社 ) 12 ( 12 ) 1677 - 1683 2000年

掲載種別: 研究論文（その他学術会議資料等）

Vg1+ gd T cells play protective roles at an early phase of MCMV infection through production of IFN-g.

Ninomiya, T., Takimoto, H., Matsuzaki, G., Hamano, S., Yoshida, H., Kimura, G., and Nomoto, K.

Immunology, ( その他の出版社 ) 99 ( 2 ) 187 - 194 2000年

掲載種別: 研究論文（その他学術会議資料等）

TCR-independent activation of extrathymically developed self antigen-specific T cells by IL-2/IL-15.

Yamada, H., Nakamura, T., Matsuzaki, G., Iwamoto, Y., and Nomoto, K.

J. Immunol. ( その他の出版社 ) 164 ( 4 ) 1746 - 1752 2000年

掲載種別: 研究論文（その他学術会議資料等）

Development of dendritic epidermal T cells with skewed diversity of gdTCRs in Vd1-deficient mice.

Hara, H., Kishihara, K., Matsuzaki, G., Takimoto, H., Tsukiyama, T., Tigelaar, R. E., and Nomoto, K.

J. Immunol. ( その他の出版社 ) 165 ( 7 ) 3695 - 3705 2000年

掲載種別: 研究論文（その他学術会議資料等）

Characterization of CD4- CD8- CD3+ T-cell receptor ab+ T cells in mouse cytomegalovirus infection.

Hossain, M. S., Takimoto, H., Ninomiya, T., Yoshida, H., Kishihara, K., Matsuzaki, G., Kimura, G., and Nomoto, K.

Immunology ( その他の出版社 ) 101 ( 1 ) 19 - 29 2000年

掲載種別: 研究論文（その他学術会議資料等）

D.R.Autospecific gd thymocytes which escape negative selection find sanctuary in the intestine.

Lin.T, Yoshida.H, Matsuzaki.G, Guehler.S.R, Nomoto.K, Barrett.T.A, Green

J.Clin.Invest. ( その他の出版社 ) 104 ( 9 ) 1297 - 1305 1999年03月

掲載種別: 研究論文（その他学術会議資料等）

The protective role of T-cell receptor Vg1+ T cells in primary infection with Listeria monocytogenes.

Nakamura.T, Matsuzaki.G, Nomoto.K

Immunology ( その他の出版社 ) 96 ( 1 ) 29 - 34 1999年03月

掲載種別: 研究論文（その他学術会議資料等）

T-Cell Hyporesponsiveness Induced by Activated Macrophages through Nitric Oxide Production in Mice Infected with Mycobacterium tuberculosis

Nabeshima.S, Nomoto.M, Matsuzaki.G, Kishihara.K, Taniguchi.H, Yoshida.S.-i, Nomoto.K

Infect. Immun. ( その他の出版社 ) 67 ( 7 ) 3221 - 3226 1999年03月

掲載種別: 研究論文（その他学術会議資料等）

The Role of B Cells in the Establishment of T Cell Response in Mice Infected with an Intracellular Bacteria, Listeria monocytogenes

Matsuzaki.G, Vordermeier.H.M, Hashimoto.A, Nomoto.K, Ivanyi.J

Cell. Immunol. ( その他の出版社 ) 194 ( 2 ) 178 - 185 1999年03月

掲載種別: 研究論文（その他学術会議資料等）

この論文にアクセスする

DOI

Escherichia coli infection induces only fetal thymus-derived γ δ T cells at the infected site

Matsuzaki.G, Takada.H, Nomoto.K

J. Immunol. ( その他の出版社 ) 29 ( 12 ) 3877 - 3886 1999年03月

掲載種別: 研究論文（その他学術会議資料等）

この論文にアクセスする

DOI

Autospecific γδ thymocytes that escape negative selection find sanctuary in the intestine

Lin, T., Yoshida, H., Matsuzaki, G., Guehler, S. R., Nomoto, K., Barrett, T. A., and Green,

J. Clin. Invest. ( その他の出版社 ) 104 ( 9 ) 1297 - 1305 1999年

掲載種別: 研究論文（その他学術会議資料等）

この論文にアクセスする

DOI

The protective role of T-cell receptor Vg1+ T cells in primary infection with Listeria monocytogenes.

Nakamura, T., Matsuzaki, G., and Nomoto, K.

Immunology, ( その他の出版社 ) 96 ( 1 ) 29 - 34 1999年

掲載種別: 研究論文（その他学術会議資料等）

T cell hyporesponsiveness induced by activated macrophages through nitric oxide production in mice infected with Mycobacterium tuberculosis.

Nabeshima, S., Nomoto, M., Matsuzaki, G., Kishihara, K., Taniguchi, H., Yoshida, S.-i., and Nomoto, K.

Infect. Immun. ( その他の出版社 ) 67 ( 7 ) 3221 - 3226 1999年

掲載種別: 研究論文（その他学術会議資料等）

The role of B cells for the establishment of T cell response in mice infected with an intracellular bacteria Listeria monocytogenes.

Matsuzaki, G., Vordermeier, H. M., Hashimoto, A., Nomoto, K., and Ivanyi, J.

Cell. Immunol. ( その他の出版社 ) 194 ( 2 ) 178 - 185 1999年

掲載種別: 研究論文（その他学術会議資料等）

Escherichia coli infection induces only fetal thymus-derived gd T cells at infected site. Eur.

Matsuzaki, G., Takada, H., and Nomoto, K.

J. Immunol. ( その他の出版社 ) 29 ( 12 ) 3877 - 3886 1999年

掲載種別: 研究論文（その他学術会議資料等）

The role of p56lck in the development of gd T cells and their function during an infection by L. monocytogenes.

Fujise.S, Matsuzaki.G, Kishihara.K, Kadena.T, Molina.T, Nomoto.K

J. Immunol. ( その他の出版社 ) 157 ( 1 ) 247 - 254 1996年03月

掲載種別: 研究論文（その他学術会議資料等）

Differential effects of viable and killed bacteria on interleukin 12 expression of macrophages.

Song.F, Matsuzaki.G, Mitsuyama.M, Nomoto.K

J. Immuonl. ( その他の出版社 ) 156 ( 8 ) 2979 - 2984 1996年03月

掲載種別: 研究論文（その他学術会議資料等）

Differential effects of viable and killed bacteria on interleukin 12 expression of macrophages.

Song, F., Matsuzaki, G., Mitsuyama, M., Nomoto, K.

J. Immuonl ( その他の出版社 ) 156 ( 8 ) 2979 - 2984 1996年03月

掲載種別: 研究論文（その他学術会議資料等）

The role of p56lck in the development of gd T cells and their function during an infection by L. monocytogenes.

Fujise, S., Matsuzaki, G., Kishihara, K., Kadena, T., Molina, T., and Nomoto, K.

J. Immunol. ( その他の出版社 ) 157 ( 1 ) 247 - 254 1996年

掲載種別: 研究論文（その他学術会議資料等）

Differential effects of viable and killed bacteria on interleukin 12 expression of macrophages.

Song, F., Matsuzaki, G., Mitsuyama, M., and Nomoto, K.

J. Immuonl. ( その他の出版社 ) 156 ( 8 ) 2979 - 2984 1996年

掲載種別: 研究論文（その他学術会議資料等）

Development of TCR-gamma delta CD4-CD8+ alpha alpha but not TCR-alpha beta CD4-CD8+ alpha alpha i-IEL is resistant to cyclosporin A

Lin.T, Matsuzaki.G, Umesue.M, Omoto.K, Yoshida.H, Harada.M, Singaram.C, Hiromatsu.K, Nomoto.K

J. Immuol. ( その他の出版社 ) 155 ( 9 ) 4224 - 4230 1995年03月

掲載種別: 研究論文（その他学術会議資料等）

Early appearance of T cell receptor αβ+ CD4− CD8− T cells with a skewed variable region repertoire after infection with Listeria monocytogenes

Matsuzaki.G, Li.X.-Y, Kadena.T, Song.F, Hiromatsu.K, Yoshida.H, Nomoto.K

Eur. J. Immunol. ( その他の出版社 ) 25 ( 7 ) 1985 - 1991 1995年03月

掲載種別: 研究論文（その他学術会議資料等）

この論文にアクセスする

DOI

Early appearance of T cell receptor ab+ CD4- CD8- T cells with a skewed variable region repertoire after infection with Listeria monocytogenes.

Matsuzaki, G., Li, X.-Y., Kadena, T., Song, F., Hiromatsu, K., Yoshida, H., and Nomoto, K.

Eur. J. Immunol. ( その他の出版社 ) 25 ( 7 ) 1985 - 1991 1995年

掲載種別: 研究論文（その他学術会議資料等）

A protective role of g/d T cells in primary infection with Listeria monocytogenes in mice.

Hiromatsu.K, Yoshikai.Y, Matsuzaki.G, Ohga.S, Muramori.K, Matsumoto.K, Bluestone.J.A, Nomoto.K

J. Exp. Med ( その他の出版社 ) 175 ( 1 ) 49 - 56 1992年03月

掲載種別: 研究論文（その他学術会議資料等）

A protective role of g/d T cells in primary infection with Listeria monocytogenes in mice.

Hiromatsu, K., Yoshikai, Y., Matsuzaki, G., Ohga, S., Muramori, K., Matsumoto, K., Bluestone, J. A. and Nomoto, K.

J. Exp. Med ( その他の出版社 ) 175 ( 1 ) 49 - 56 1992年

掲載種別: 研究論文（その他学術会議資料等）

　前のページ-次のページ　

<松崎 吾朗>

論文 - 松崎 吾朗

<松崎　吾朗>

論文 - 松崎　吾朗