转化生长因子β信号在天然CD4+CD25+Foxp3+调节性T细胞发育中的关键作用。
A critical function for TGF-beta signaling in the development of natural CD4+CD25+Foxp3+ regulatory T cells.
作者信息
Liu Yongzhong, Zhang Pin, Li Jun, Kulkarni Ashok B, Perruche Sylvain, Chen Wanjun
机构信息
Mucosal Immunology Unit, Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA.
出版信息
Nat Immunol. 2008 Jun;9(6):632-40. doi: 10.1038/ni.1607. Epub 2008 Apr 27.
The molecular mechanisms directing the development of 'natural' CD4+CD25+Foxp3+ regulatory T cells (T(reg) cells) in the thymus are not thoroughly understood. We show here that conditional deletion of transforming growth factor-beta receptor I (TbetaRI) in T cells blocked the appearance of CD4+CD25+Foxp3+ thymocytes at postnatal days 3-5. Paradoxically, however, beginning 1 week after birth, the same TbetaRI-mutant mice showed accelerated expansion of thymic CD4+CD25+Foxp3+ populations. This rapid recovery of Foxp3+ thymocytes was attributable mainly to overproduction of and heightened responsiveness to interleukin 2, as genetic ablation of interleukin 2 in TbetaRI-mutant mice resulted in a complete absence of CD4+CD25+Foxp3+ cells from the thymus and periphery. Thus, transforming growth factor-beta signaling is critical to the thymic development of natural CD4+CD25+Foxp3+ T(reg) cells.
指导胸腺中“天然”CD4+CD25+Foxp3+调节性T细胞（Treg细胞）发育的分子机制尚未完全明确。我们在此表明，T细胞中转化生长因子-β受体I（TβRI）的条件性缺失在出生后第3至5天阻断了CD4+CD25+Foxp3+胸腺细胞的出现。然而，矛盾的是，出生1周后，相同的TβRI突变小鼠胸腺CD4+CD25+Foxp3+群体出现加速扩增。Foxp3+胸腺细胞的这种快速恢复主要归因于白细胞介素2的过量产生和对其反应性增强，因为TβRI突变小鼠中白细胞介素2的基因缺失导致胸腺和外周完全没有CD4+CD25+Foxp3+细胞。因此，转化生长因子-β信号对于天然CD4+CD25+Foxp3+Treg细胞的胸腺发育至关重要。
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