The Wistar Institute, Philadelphia, PA 19104, USA.
J Leukoc Biol. 2010 Dec;88(6):1099-107. doi: 10.1189/jlb.0310183. Epub 2010 May 21.
The cataclysmic disease that develops in mice and humans lacking CD4+ T cells expressing the transcription factor Foxp3 has provided abundant evidence that Foxp3+CD4+ Tregs are required to suppress a latent autoreactivity of the immune system. There is also evidence for the existence of tissue-specific Tregs that can act to suppress regional autoimmune responses, suggesting that Tregs exert their effects, in part, through responding to self-peptides. However, how the immune system generates a repertoire of Tregs that is designed to recognize and direct regulatory function to self-peptides is incompletely understood. This review describes studies aimed at determining how T cell recognition of self-peptide(s) directs Treg formation in the thymus, including discussion of a modified "avidity" model of thymocyte development. Studies aimed at determining how TCR specificity contributes to the ability of Tregs to suppress autoimmune diseases are also discussed.
在缺乏表达转录因子 Foxp3 的 CD4+T 细胞的小鼠和人类中发生的灾难性疾病提供了丰富的证据，表明 Foxp3+CD4+Treg 是抑制免疫系统潜伏自身反应所必需的。也有证据表明存在组织特异性 Treg，可抑制局部自身免疫反应，这表明 Treg 通过响应自身肽发挥作用。然而，免疫系统如何产生一组旨在识别和指导自身肽的调节功能的 Treg 尚不完全清楚。这篇综述描述了旨在确定 T 细胞对自身肽的识别如何在胸腺中指导 Treg 形成的研究，包括对胸腺细胞发育的改良“亲和力”模型的讨论。还讨论了旨在确定 TCR 特异性如何有助于 Treg 抑制自身免疫性疾病的能力的研究。
