| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2001: ¥2,900,000 (Direct Cost: ¥2,900,000)
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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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