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J Leukoc Biol. 2010 Dec;88(6):1099-107. doi: 10.1189/jlb.0310183. Epub 2010 May 21.

How specificity for self-peptides shapes the development and function of regulatory T cells.

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  • 1The Wistar Institute, Philadelphia, PA 19104, USA.


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.

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