Induction and maintenance of self tolerance: the role of CD4+CD25+ regulatory T cells.
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-2Ralpha 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.
Bala
Kamalesh K
KK
Department of Microbiology and Immunology, University of Maryland School of Medicine, Howard Hall 323C, 660 W. Redwood St., Baltimore, MD 21201, USA.
Moudgil
Kamal D
KD
D000818:Animals; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D051379:Mice; D017634:Self Tolerance / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit