Abstract.
The immune system responds vigorously to invading pathogens (non-self, foreign), while remaining unresponsive (tolerant) to the body’s own components and circulating constituents (self). This indifference to self components is a result of finely orchestrated events of thymic negative selection (central tolerance) of developing T cells that are autoaggressive combined with those operative in the periphery (peripheral tolerance) to control the activity of potentially autoreactive T cells that escaped thymic tolerance. Recently, autoimmune regulator expressed in the thymus has been identified as a critical mediator of central tolerance towards tissue-specific antigens. In the periphery, a variety of regulatory T cells are involved in effecting tolerance. There is immense interest and excitement about the newly identified subset of CD4+CD25+ T cells. This is a unique subset of CD4+ T cells that bear CD25 (IL-2Rα chain) on the cell surface in the naïve state and express FoxP3 as a unique marker. These cells suppress the activity of autoreactive effector T cells primarily via cell-cell contact. The deficiency and/or altered function of CD4+CD25+ T cells is associated with autoimmunity. Mice deficient in FoxP3 (scurfy mice) bear an autoimmune phenotype, and human males with mutations in the corresponding gene express the phenotype of wide-spread autoimmunity, the immune dysregulation, polyendocrinopathy and enteropathy, and X-linked syndrome. In vitro expansion of antigen-specific CD4+CD25+ T cells and their adoptive transfer into patients suffering from autoimmunity is emerging as a promising new therapeutic approach for these debilitating disorders.
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Bala, K.K., Moudgil, K.D. Induction and maintenance of self tolerance: the role of CD4+CD25+ regulatory T cells. Arch. Immunol. Ther. Exp. 54, 307–321 (2006). https://doi.org/10.1007/s00005-006-0035-x
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DOI: https://doi.org/10.1007/s00005-006-0035-x