NK T cell-derived IL-10 is essential for the differentiation of antigen-specific T regulatory cells in systemic tolerance
NK T cell-derived IL-10 is essential for the differentiation of antigen-specific T regulatory cells in systemic tolerance
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DOI：
10.4049/jimmunol.166.1.42
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发表时间：
2001-01-01
影响因子：
4.4
通讯作者：
Stein-Streilein, J
中科院分区：
文献类型：
--
作者：
Sonoda, KH;Faunce, DE;Stein-Streilein, J
在一种称为前房相关免疫偏差（ACAID）的全身耐受模型中，T调节（Tr）细胞的分化依赖于NK T细胞，发生在脾脏。我们现在发现，由于J α 281敲除（KO）小鼠无法产生ag特异性Tr细胞和ACAID，因此cd1反应性NK T细胞亚群表达不变的V α 14J α 281 TCR。通过定义异质和富集NK T脾细胞中的细胞因子谱，研究了NK T细胞依赖ag特异性Tr细胞分化介导系统性耐受性的机制。与大多数调节性细胞因子mRNA无差异相比，IL-10 mRNA和蛋白在前房（a.c）接种小鼠脾NK T细胞中均升高。而IL-10 mRNA在灌胃后未见明显升高。最后，野生型（WT）小鼠的NK T细胞，而不是IL-10 KO小鼠的NK T细胞，在J α 281 KO小鼠中重建了ACAID诱导能力。因此，NK T细胞衍生的IL-10对于ag特异性Tr细胞的产生和眼接种ag诱导的全身耐受至关重要。
In a model of systemic tolerance called Anterior Chamber-Associated Immune Deviation (ACAID), the differentiation of the T regulatory (Tr) cells depends on NK T cells and occurs in the spleen. We now show that the CD1d-reactive NK T cell subpopulation, required for development of systemic tolerance, expresses the invariant V alpha 14J alpha 281 TCR because J alpha 281 knockout (KO) mice were unable to generate Ag-specific Tr cells and ACAID, The mechanism for NK T cell-dependent differentiation of Ag-specific Tr cells mediating systemic tolerance was studied by defining the cytokine profiles in heterogeneous and enriched NK T spleen cells. In contrast to there being no differences in most regulatory cytokine mRNAs, both mRNA and protein for IL-10 were increased in splenic NK T cells of anterior chamber (a.c.)-inoculated mice. However, IL-10 mRNA was not increased in spleens after i.v. inoculation. Finally, NK T cells from wild-type (WT) mice, but not from IL-10 KO mice, reconstituted the ACAID inducing ability in J alpha 281 KO mice. Thus, NK T cell-derived IL-10 is critical for the generation of the Ag-specific Tr cells and systemic tolerance induced to eye-inoculated Ags.