1999 Fiscal Year Final Research Report Summary
Molecular basis of type2 helper T cell differentiation reading to lgE production
| Project/Area Number |
10670311
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Immunology
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| Research Institution | Chiba University |
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Principal Investigator |
NAKAYAMA Toshinori Chiba University, Graduate School of Medicine, Associate Professor, 大学院・医学研究科, 助教授 (50237468)
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| Project Period (FY) |
1998 – 1999
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| Keywords | Th1 / Th2 / Ras / MARK cascade / allergy / T cell receptor |
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| Research Abstract |
The central role of Type-2 helper T (Th2) cells in the development of allergic responses and immune responses against helminthic parasites is well documented. The differentiation of Th2 cells from naive T cells requires both the recognition of antigen by T-cell antigen receptors (TCR) and the activation of downstream signal transduction molecules of the IL-4 receptor (IL-4R) pathway, including Jak1, Jak3, and STAT6. Little is known, however, about how these two distinct pathways cooperate with each other to induce Th2 cells. Here we use a T cell specific H-ras-dominant negative transgenic mouse to show that TCR-mediated activation of Ras/Mitogen-activated protein kinase (MAPK) pathway alters IL-4R function and is required for Th2 cell differentiation. The enhancement of IL-4R signaling appears to be a consequence of both direct crosstalk with the TCR signaling pathway and increased protein expression of downstream signaling molecules of the IL-4R pathway. Therefore, successful Th2 differentoation depends on the effectiveness of the TCR-mediated activation of the Ras/MAPK pathways in modifying the IL-4R-mediated signaling pathway. In another words, we present evidence that the TCR-mediated Ras/MAPK activation controls IL4R-mediated signaling and determines the direction of helper T cell differentiation. Thus, our data suggest that the lineage choices made by naive Th cells following antigen, stimulation are clearly influenced by.
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[Publications] Yamashita, M., Hashimoto, K., Kimura, M., Kubo, M., Tada, T. and Nakayama, T.: "Requirement for p56/ck tyrosine kinase activation in T helper subset differentiation."Int. Immunol.. 10. 577-591 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Kawano, T., Cui, J., Koezuka, Y., Toura, I., Kaneko, Y., Sato, H., Kondo, E., Harada, M., Koseki, H., Nakayama, T., Tanaka, Y., and Taniguchi, M.: "Natural killer-like nonspecific tumor cell lysis mediated by specific ligand-activated Va14 NKT cells."Proc. Natl. Acad. Sci. USA.. 95. 5690-5693 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Yamashita, M., Kimura, M., Kubo, M., Shimizu, C., Tada, T., Perlmutter, R. M., and Nakayama, T.: "TCR-mediated activation of Ras/MAPK pathway controls IL-4 receptor function and Th2 cell differentiation."Proc. Natl. Acad. Sci. USA. 96. 1024-1029 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Sato, H., Nakayama, T., Tanaka, Y., Yamashita, M., Shibata, Y., Kondo, E., Saito, Y., and Taniguchi, M.: "Induction of differentiation of pre-NKT cells to mature Va14 NKT cells by GM-CSF."Proc. Natl. Acad. Sci. USA. 96. 7439-7444 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Kubo, M., Yamashita, M., Tada, T., Abe, R., Okumura, K., Ransom, J. T., and Nakayama, T.: "T cell receptor stimulation and CD28 costimulation increases IL-4 receptor sensitivity : A requirement for Th2 differentiation."J. Immunol.. 163. 2432-2442 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Cui, J., Watanabe, N., Kawano, T., Yamashita, Y., Kamata, T., Shimizu, C., Kimura, M., Shimizu, E., Koike, J., Koseki, H., Tahaka, Y., Taniguchi, M., and Nakayama, T.: "Inhibition of Th2 cell differentiation and lgE response by ligand-activated Va14 NKT cells."J. Exp. Med.. 190. 783-792 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Kaneko, Y., Harada, M., Kawano, T., Yamashita, M., Shibata, Y., Geiyo, F., Nakayama, T., and Taniguchi M.: "Augmentation of Va14 NKT Cell-mediated Cytotoxicity by IL-4 in an Autocrine Mechanism Resulting in the Development of Concanavalin A-induced Hepatitis."J. Exp. Med.. 191. 105-114 (2000)
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「研究成果報告書概要(欧文)」より
