論文 - 松崎　吾朗

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）

　概要を見る

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.

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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）

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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）

　概要を見る

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.

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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）

　概要を見る

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.

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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）

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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）

　概要を見る

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.

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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）

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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.

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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）

　概要を見る

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.

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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）

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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）

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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）

　概要を見る

<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>

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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）

　概要を見る

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.

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  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）

　概要を見る

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.

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）

　概要を見る

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.

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