2003 Fiscal Year Final Research Report Summary
Regulatory mechanism of homeostatic T cell proliferation
| Project/Area Number |
14599011
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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 |
細胞死(アポトーシス)
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| Research Institution | AKITA UNIVERSITY |
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Principal Investigator |
OHTEKI Toshiaki Akita University, School of Medicine, Professor, 医学部, 教授 (50233200)
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| Project Period (FY) |
2002 – 2003
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| Keywords | CTLA-4 / IL-2 / IL-2R / T cell activation / autoimmune disease / human / mouse |
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| Research Abstract |
Cytotoxic T lymphocyte-associated molecule-4 (CTLA-4) transduces inhibitory signals for T cell activation and regulates T cell homeostasis in vivo. Indeed, mice deficient for CTLA-4 exhibit lymphoproliferative autoimmune disease and early death at 3-4 wk of age. We show that T cells activated in the absence of IL-2/IL-2R interaction fail to express CTLA-4 on the cell surface. The lack of surface expression is due to impaired mRNA expression but not to a defect in protein trafficking. Our results demonstrate that IL-2 is essential for CTLA-4 induction in activated T cells, and suggest that the impairment of CTLA-4 induction is one of mechanisms causing fatal autoimmune disease observed in mice lacking IL-2/IL-2R system in vivo.
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[Publications] Honda, K., Sakaguchi, S., Nakajima, C., Watanabe, A., Yanai, H., Matsumoto, M., Ohteki, T., Kaisho, T., Takaoka, A., Akira, S., Seya, T., Taniguchi, T.: "Selective contribution of IEN-α/β signaling to the maturation of dendritic cells induced by double-stranded RNA or viral infection."Proc.Natl.Acad.Sci.USA.. 100. 10872-10877 (2003)
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「研究成果報告書概要(欧文)」より
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[Publications] Yamauchi, T., Kamon, J., Ito, Y., Tsuchida, A., Yokomizo, T., Kita, S., Sugiyama, T., Miyagishi, M., Hara, K., Tsunoda, M., Murakami, K., Ohteki, T., Uchida, S., Takekawa, S., Waki, H., Tsuno, N.H., Shibata, Y., Terauchi, Y., Froguel, P., Tobe, K., Koyasu, S., Taira, K., Kitamura, T., Shimizu, T., Nagai, R., Kadowaki, T.: "Cloning of adiponectin receptors that mediated antidiabetic metabolic effects."Nature. 423. 762-769 (2003)
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[Publications] Saibil^*, S.D., Ohteki^*, T., (^*equal contribution) White, F.M., Luscher, M., Zakarian, A., Elford, A., Shabanowitz, J., Nishina, H., Hugo, P., Penninger, J., Barber, B., Hunt, D.F., Ohashi, P.S.: "Weak agonist self-peptides promote selection and tuning of virus-specific T cells."Eur.J.Immunol.. 33. 685-696 (2003)
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[Publications] Suzuki, H., Matsuda, S., Terauchi, Y., Fujiwara, M., Ohteki, T., Asano, T., Behrens, T.W., Kouro, T., Takatsu, K., Kadowaki, T., Shigeo Koyasu: "PI3K and Btk differentially regulate B cell antigen receptor mediated signal transduction."Nat.Immunol.. 4. 280-286 (2003)
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[Publications] Garza, K., McKall-Faienza, K., Ohteki, T., Zakarian, A., Odermatt, B., Ohashi, P.: "Enhanced T cell responses contribute to the genetic predisposition of CD8-mediated spontaneous autoimmunity."Eur.J.Immunol.. 32. 885-894 (2002)
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