AUTOIMMUNITY part 60

Regulatory T cells (Treg) also play an important role in maintaining peripheral tolerance. Several different subsets of Treg have been reported, but one of the most intensely studied is the CD4CD25Foxp3 subset, which represent about 10% of total CD4 cells. These cells regulate T-cell activation by a cell-cell contact dependent mechanism and through the secretion of inhibitory cytokines such as IL-10 and transforming growth factor-beta (TGFβ). They suppress both naive and memory T-cell responses and down-regulate the expression of pro-inflammatory cytokines and co-stimulatory molecules on the antigen-presenting cells. These cells are induced in an antigen specific manner, but the subsequent suppressive effects are not antigen specific. Genetic defects in Foxp3, a transcription factor that is the key controller of Treg function, lead to organ specific autoimmune or autoinflammatory diseases. The scurfy mouse has an X-linked defect of the Foxp3 gene that is lethal in males, which exhibit hyperactivation of CD4 T cells and overproduction of inflammatory cytokines. Foxp3 mutations in humans are the cause of the IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome) syndrome. These individuals develop organ specific autoimmune diseases, such as TID, autoimmune thyroiditis, and inflammatory bowel disease. Interestingly, however, the development of systemic autoimmune disease is not part of the syndrome in either mice or humans