University of Munich, Institute for Immunology, Goethestr. 31, 80336 Munich, Germany.
Semin Immunol. 2011 Dec;23(6):401-9. doi: 10.1016/j.smim.2011.06.003. Epub 2011 Jul 6.
A substantial fraction of the Foxp3(+) CD4(+) regulatory T (T(reg)) cell repertoire is generated through instructive and/or selective processes in the thymus, and there is some consensus that clonal deviation into the T(reg) lineage is a result of self-antigen recognition. Paradoxically, the same holds true for a diametrically different cell fate decision of developing thymocytes, namely their removal from the repertoire through apoptotic cell death (clonal deletion). Here, we will review our current understanding of how T cell receptor stimulation, cytokine signaling, co-stimulation, epigenetic modifications and T cell intrinsic developmental tuning synergize during T(reg) cell differentiation, and how instructive signals converge at the Foxp3 gene-locus during entry into the T(reg) cell lineage. We will also discuss how these parameters relate to known determinants of negative selection.
Foxp3(+) CD4(+) 调节性 T（T(reg)）细胞库的很大一部分是通过胸腺中的指令性和/或选择性过程产生的，并且人们普遍认为，克隆偏离 T(reg)谱系是自身抗原识别的结果。矛盾的是，对于胸腺细胞的另一种截然不同的细胞命运决定，即通过凋亡细胞死亡（克隆删除）从库中去除，情况也是如此。在这里，我们将回顾我们目前对 T 细胞受体刺激、细胞因子信号、共刺激、表观遗传修饰和 T 细胞内在发育调节如何在 T(reg)细胞分化过程中协同作用的理解，以及指令性信号如何在进入 T(reg)细胞谱系时汇聚在 Foxp3 基因座上。我们还将讨论这些参数与已知的阴性选择决定因素有何关系。
