Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
Semin Immunopathol. 2010 Jun;32(2):95-106. doi: 10.1007/s00281-010-0200-5. Epub 2010 Feb 24.
Naturally arising CD4(+)CD25(+) regulatory T cells (Treg cells), which specifically express the forkhead family transcription factor Foxp3, are essential for the maintenance of immunological self-tolerance and immune homeostasis. Stimulation of the T cell antigen receptor (TCR) via recognizing self-peptide/major histocompatibility complex (MHC) is required for their expression of Foxp3 in the course of their development in the thymus. The TCR repertoires displayed by Treg cells and naïve T cells are apparently distinct, suggesting that Treg cells with high reactivity to self-peptide/MHC ligands are somehow driven to Treg cell lineage in the thymus. Treg cells also require stimulation via TCR to exert suppression in the periphery. At the molecular level, assembly of Foxp3, Foxp3-interacting factors, and chromatin-remodeling factors is in part under the control of TCR signaling, and TCR stimulation alters Foxp3-dependent transcriptional regulation, protein-protein interaction, and Foxp3 recruitment to the specific genomic loci. These findings collectively indicate that the TCR signaling is essential for suppressive function of Treg cells and that TCR has a determinant role for driving developing T cells to the Foxp3(+)CD4(+)CD25(+) Treg cell lineage and differentiation.
天然产生的 CD4(+)CD25(+)调节性 T 细胞（Treg 细胞），其特异性表达叉头框家族转录因子 Foxp3，对于维持免疫耐受和免疫稳态至关重要。在胸腺中发育过程中，T 细胞抗原受体（TCR）通过识别自身肽/MHC 来刺激 T 细胞表达 Foxp3。Treg 细胞和幼稚 T 细胞所展示的 TCR 谱系显然不同，这表明对自身肽/MHC 配体具有高反应性的 Treg 细胞以某种方式被驱动到胸腺中的 Treg 细胞谱系中。Treg 细胞也需要通过 TCR 刺激在外周发挥抑制作用。在分子水平上，Foxp3、Foxp3 相互作用因子和染色质重塑因子的组装部分受到 TCR 信号的控制，并且 TCR 刺激改变了 Foxp3 依赖性转录调控、蛋白质-蛋白质相互作用和 Foxp3 募集到特定的基因组位点。这些发现共同表明 TCR 信号对于 Treg 细胞的抑制功能至关重要，并且 TCR 对于驱动发育中的 T 细胞向 Foxp3(+)CD4(+)CD25(+)Treg 细胞谱系和分化具有决定作用。
