Li Ming O, Sanjabi Shomyseh, Flavell Richard A
Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Immunity. 2006 Sep;25(3):455-71. doi: 10.1016/j.immuni.2006.07.011.
The role of transforming growth factor-beta (TGF-beta) in inhibiting T cell functions has been studied with dominant-negative TGF-beta receptor transgenic models; however, the full impact of TGF-beta signaling on T cells and the mechanisms by which TGF-beta signals remain poorly understood. Here we show that mice with T cell-specific deletion of TGF-beta receptor II developed lethal inflammation associated with T cell activation and differentiation. In addition, TGF-beta signaling positively regulated T cell development and homeostasis. Development of CD8+ T cells and NKT cells, maintenance of peripheral Foxp3-expressing regulatory T cells, and survival of CD4+ T cells all depended on TGF-beta signaling. Both T helper 1 (Th1) differentiation and survival of activated CD4+ T cells required T-bet, the TGF-beta-regulated transcription factor, which controlled CD122 expression and IL-15 signaling in Th1 cells. This study reveals pleiotropic functions of TGF-beta signaling in T cells that may ensure a diverse and self-tolerant T cell repertoire in vivo.
利用显性负性转化生长因子-β（TGF-β）受体转基因模型对TGF-β在抑制T细胞功能中的作用进行了研究；然而，TGF-β信号传导对T细胞的全面影响以及TGF-β信号传导的机制仍知之甚少。在此我们表明，T细胞特异性缺失TGF-β受体II的小鼠发生了与T细胞活化和分化相关的致死性炎症。此外，TGF-β信号传导正向调节T细胞发育和稳态。CD8+T细胞和自然杀伤T（NKT）细胞的发育、外周表达叉头框蛋白3（Foxp3）的调节性T细胞的维持以及CD4+T细胞的存活均依赖于TGF-β信号传导。辅助性T细胞1（Th1）分化以及活化的CD4+T细胞的存活均需要T-bet，即TGF-β调节的转录因子，其控制Th1细胞中CD122的表达和白细胞介素-15（IL-15）信号传导。本研究揭示了TGF-β信号传导在T细胞中的多效性功能，这可能确保体内存在多样化且自我耐受的T细胞库。
