論文 - 松崎　吾朗

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）

　概要を見る

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.

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  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）

　概要を見る

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.

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  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）

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  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）

　概要を見る

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.

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  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）

　概要を見る

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.

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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）

　概要を見る

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.

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  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）

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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）

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  DOI