Regulatory T cells have been shown to prevent the development of autoimmune disease, and can modulate immune responses during infections or following tissue transplantation. Recently, the processes by which CD4+CD25+ regulatory T cells are produced during immune repertoire formation have begun to be elucidated. This review focuses on the role of self-peptides in mediating CD4+CD25+ regulatory T cell selection in the thymus. How self-peptides continue to have an important influence on the accumulation of CD4+CD25+ regulatory T cells in the periphery is also discussed.
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