Essential role for STAT5 signaling in CD25+CD4+ regulatory T cell homeostasis and the maintenance of self-tolerance
Essential role for STAT5 signaling in CD25+CD4+ regulatory T cell homeostasis and the maintenance of self-tolerance
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DOI：
10.4049/jimmunol.171.7.3435
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发表时间：
2003-10-01
影响因子：
4.4
通讯作者：
Van Parijs, L
中科院分区：
文献类型：
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作者：
Antov, A;Yang, L;Van Parijs, L
CD25(+)CD4(+)调节性T细胞(T Regs)通过抑制自身反应性T细胞反应来维持自身免疫耐受。在健康小鼠的外周淋巴组织中，CD25(+)、CD4(+)T细胞的数量很少，但数量稳定。最近的研究表明，IL-2是这些细胞必不可少的生长因子。这种细胞因子是如何调节CD25(+)、CD4(+)T细胞调节平衡和预防自身免疫性疾病的，目前尚不清楚。在传统的CD4(+)T细胞中，IL-2通过激活STAT5转录因子和增加抗凋亡蛋白Bcl-2的表达来触发促进增殖和存活的信号通路。我们发现bcl2缺乏并不影响CD25(+)CD4(+)T细胞的稳态，并且该分子的异位表达不能挽救CD25(+)CD4(+)T细胞的数量，也不能阻止IL-2缺陷小鼠自身免疫的发展。此外，瞬时激活STAT5足以增加IL-2缺陷小鼠CD25(+)CD4(+)T细胞的数量。我们的研究揭示了STAT5在维持CD25(+)、CD4(+)T调节基因动态平衡和自我耐受方面的重要作用。
A population of CD25(+)CD4(+) regulatory T cells (T regs) functions to maintain immunological self tolerance by inhibiting auto-reactive T cell responses. CD25(+)CD4(+) T regs are present in low, but steady, numbers in the peripheral lymphoid tissues of healthy mice. Recent studies have shown that IL-2 is an essential growth factor for these cells. How this cytokine functions to regulate CD25(+)CD4(+) T reg homeostasis and prevent autoimmune disease remains unknown. In conventional CD4(+) T cells, IL-2 triggers signaling pathways that promote proliferation and survival by activating the STAT5 transcription factor and by increasing the expression of the antiapoptotic protein, Bcl-2. We show here that bcl-2 deficiency does not affect CD25(+)CD4(+) T reg homeostasis, and that ectopic expression of this molecule fails to rescue CD25(+)CD4(+) T reg numbers or to prevent the development of autoimmunity in IL-2-deficient mice. Furthermore, transient activation of STAT5 is sufficient to increase CD25(+)CD4(+) T reg numbers in IL-2-deficient mice. Our study uncovers an essential role for STAT5 in maintaining CD25(+)CD4(+) T reg homeostasis and self-tolerance.