2002 Fiscal Year Final Research Report Summary
Studies on the regulatory mechanisms of type I interferons for T cell functions.
| Project/Area Number |
13670313
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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 | Shinshu University (2002)
Chiba University (2001) |
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Principal Investigator |
TAKI Shinsuke Shinshu University, Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (50262027)
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| Project Period (FY) |
2001 – 2002
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| Keywords | interferons / signal transaction / receptors / CD4+ T cells / CD8+ T cells / Th1 / Th2 / memory T cells / interlenkin-4 |
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| Research Abstract |
CD4+ T cells in mice lacking the transcription factor interferon regulatory factor (IRF)-2, which we have shown to be a physiological negative regulator of the type I interferon (IFN-α/β) system, exhibited Th2 shift. We established here IRF-2-deficient mice expressing DO11.10 T cell receptor transgene, and examined in detail Th1/Th2 differentiation of CD4+ T cells in these mice. We found that IRF-2-deficient CD4+ T cells themselves were normal in terms of Th1/Th2 differentiation, and instead the environment wherein CD4+ T cells undergo differentiation affected the Th1/Th2 balance, and that splenic basophils produce initial IL-4, thereby inducing the Th2 shift. In mice lacking IRF-2 and the IFN-α/β receptor, basophils did not produce much IL-4, whereas in mice lacking both IRF-2 and signal transducer and activator of transcription (STAT)-6, the initial IL-4 production was not diminished. These results indicate that the Th2 shift in IRF-2-deficient mice is dependent oa IFN-α/β signals but not IL-4/IL-13. On the other hand, polydonal memory phenotype CD4+ and CD8+ T cells were accumulated in IRF-2-deficient mice to a higher extent than in wild-type mice within several months after birth, indicating that IRF-2 plays a role in regulating memory T cell homeostasis. We found that IRF-2 functions in a T cell-intrinsic manner, independent of continuous stimulation with endogenous or environmental antigens. Moreover, the mechanism for the memory T cell regulation by IRF-2 was found to be a novel one, distinct from that for the regulation of IFN-α/β signals.
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Research Products
(8 results)
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[Publications] Yokosuka, T., Takase, K, Suzuki, M., Nakagawa, Y., Taki, S., Takahashi, H., Fujisawa, T., Arase, H. and Saito, T.: "Predominant Role of T Cell Receptor (TCR)-α Chain in Forming Preimmune TCR Repertoire Revealed by Clonal TCR Reconstitution System."J. Exp. Med.. 195. 991-1001 (2002)
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「研究成果報告書概要(欧文)」より
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[Publications] Ichii, H., Sakamoto, A., Hatano, M., Okada, S., Toyama, H., Taki, S., Arima, M., Kuroda, Y. and Tokuhisa, T.: "Role for Bcl-6 in the generation and maintenance of memory CD8+ T cells."Nat. Immunol.. 3. 558-563 (2002)
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[Publications] Miura-Shimura, Y., Nakamura, K., Ohtsuji, M., Tomita, H., Jiang, Y., Abe, M., Zhang, D., Hamano, Y., Tsuda, H., Hashimoto, H., Nishimura, H., Taki, S., Shirai, T. and Hirose S.: "C1q regulatory region polymorphism down-regulating murine Clq protein levels with linkage to lupus nephritis."J. Immunol.. 169. 1334-1339 (2002)
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「研究成果報告書概要(欧文)」より
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