Studies on the regulatory mechanisms of type I interferons for T cell functions.

转录因子干扰素调节因子(IRF)-2是I型干扰素（IFN-α/β）系统的生理负调节因子，在缺乏转录因子干扰素调节因子(IRF)-2的小鼠中，CD4+ T细胞表现出Th2移位。我们建立了表达DO11.10 T细胞受体转基因的irf -2缺陷小鼠，并详细检测了这些小鼠CD4+ T细胞的Th1/Th2分化。我们发现irf -2缺陷的CD4+ T细胞本身在Th1/Th2分化方面是正常的，相反，CD4+ T细胞进行分化的环境影响了Th1/Th2的平衡，并且脾嗜碱性细胞产生初始的IL-4，从而诱导Th2的转移。在缺乏IRF-2和IFN-α/β受体的小鼠中，嗜碱性细胞不产生大量的IL-4，而在缺乏IRF-2和信号传导和转录激活因子(STAT)-6的小鼠中，初始IL-4的产生并未减少。这些结果表明，irf -2缺陷小鼠的Th2转移依赖于IFN-α/β信号，而不依赖于IL-4/IL-13信号。另一方面，与野生型小鼠相比，IRF-2缺陷小鼠在出生后几个月内积累了更多的多体记忆表型CD4+和CD8+ T细胞，这表明IRF-2在调节记忆T细胞稳态中起作用。我们发现IRF-2以T细胞固有的方式发挥作用，独立于内源性或环境抗原的持续刺激。此外，IRF-2调节记忆T细胞的机制与IFN-α/β信号的调节机制不同。

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.