Almost every type of lymphocyte has been shown to display regulatory activity in some circumstance. Even B cells can regulate experimentally induced autoimmune syndromes, including collagen-induced arthritis (CIA) and EAE. This activity is probably mediated in a similar way to that of regulatory CD4 T cells, with the secretion of cytokines that inhibit proliferation and differentiation of effector T cells.
In addition to the extrinsic regulation of autoreactive T and B cells by regulatory cells, lymphocytes have intrinsic proliferation and survival limits that can help restrict autoimmune as well as normal responses (see Section 11-16). This is illustrated by the development of spontaneous autoimmunity that is caused by mutations in pathways that control apoptosis, such as the Bcl-2 pathway or the Fas pathway (see Section 7-23); mutations in these pathways lead to spontaneous autoimmunity. This form of autoimmunity provides evidence that autoreactive cells are normally generated but are then eliminated by apoptosis. This seems to be an important mechanism for both Tand B-cell tolerance.
periphery thymus periphery Cytokines (IL-10 and TGF-˜) produced by Treg cells inhibit other self-reactive T cells TGF-˜Regulatory tolerance T cell specifc for self antigen recognized in thymus becomes a natural regulatory T cell (nTreg) T cell specifc for self or commensal microbiota antigen recognized in presence of TGF-˜becomes an induced regulatory T cell (iTreg)
Fig. 15.9 Tolerance mediated by regulatory T cells can inhibit multiple autoreactive T cells that all recognize antigens from the same tissue.
Specialized autoreactive natural regulatory T (nTreg) cells develop in the thymus in response to stimulation by self antigens that is too weak to cause deletion but is greater than required for simple positive selection (upper left panel). Regulatory T cells can also be induced from naive self‑reactive T cells in the periphery if the naive T cell recognizes its antigen and is activated in the presence of the cytokine TGF‑β (upper right panel). The lower panel shows how regulatory T cells, both natural and induced, can inhibit other self‑reactive T cells. If regulatory T cells encounter their self antigen on an antigen‑presenting cell, they secrete inhibitory cytokines such as IL‑10 and TGF‑β that inhibit all surrounding autoreactive T cells, regardless of their precise autoantigen specificity.
Summary.