Chen WanJun, Konkel Joanne E
Mucosal Immunology Section, OPCB, NIDCR, 30 Convent Dr., Bethesda, MD, USA.
Eur J Immunol. 2015 Apr;45(4):958-65. doi: 10.1002/eji.201444999. Epub 2015 Mar 18.
CD4(+) regulatory T cells expressing the transcription factor Foxp3 can be generated in the thymus (tTreg cells), but the cellular and molecular pathways driving their development remain incompletely understood. TGF-β is essential for the generation of Foxp3(+) Treg cells converted from peripheral naïve CD4(+) T cells (pTreg cells), yet a role for TGF-β in tTreg-cell development was initially refuted. Nevertheless, recent studies have unmasked a requirement for TGF-β in the generation of tTreg cells. Experimental evidence reveals that TGF-β in the context of TCR stimulation induces Foxp3 gene transcription in thymic Treg precursors, CD4(+) CD8(-) CD25(-) semimature and mature single-positive thymocytes. Intriguingly, thymic apoptosis was found to be intrinsically linked to the generation of tTreg cells, as apoptosis induced expression of TGF-β intrathymically. In this short review, we will highlight key data, discuss the experimental evidence and propose a modified model of tTreg-cell development involving TGF-β. We will also outline the remaining unresolved questions concerning generation of thymic Foxp3(+) Treg cells and provide our personal perspectives on the mechanisms controlling tTreg-cell development.
表达转录因子Foxp3的CD4(+)调节性T细胞可在胸腺中产生（胸腺来源的调节性T细胞），但其发育的细胞和分子途径仍未完全明确。转化生长因子-β（TGF-β）对于外周幼稚CD4(+) T细胞转化而来的Foxp3(+)调节性T细胞（外周来源的调节性T细胞）的产生至关重要，然而TGF-β在胸腺来源的调节性T细胞发育中的作用最初遭到否定。尽管如此，最近的研究揭示了TGF-β在胸腺来源的调节性T细胞产生过程中的必要性。实验证据表明，在TCR刺激的背景下，TGF-β可诱导胸腺调节性T细胞前体、CD4(+) CD8(-) CD25(-)半成熟和成熟单阳性胸腺细胞中的Foxp3基因转录。有趣的是，胸腺凋亡被发现与胸腺来源的调节性T细胞的产生存在内在联系，因为凋亡可诱导胸腺内TGF-β的表达。在这篇简短的综述中，我们将重点介绍关键数据，讨论实验证据，并提出一个涉及TGF-β的胸腺来源的调节性T细胞发育的修正模型。我们还将概述关于胸腺Foxp3(+)调节性T细胞产生的尚未解决的问题，并提供我们对控制胸腺来源的调节性T细胞发育机制的个人观点。
