Peripheral self-tolerance and autoimmunity: the protective role of expression of class II major histocompatibility antigens on non-lymphoid cells.
Immunologic self-tolerance is achieved mainly during development by clonal deletion in the thymus of T lymphocytes with receptors specific for self-antigens and with associated T-cell markers CD4/CD8. However, T cells expressing a low level of these markers are allowed into the periphery still bearing their autospecific receptors. Such clonal deletion, induced by cells bearing the class II antigens coded for by major histocompatibility complex (MHC) in the thymus, does not remove all autoreactive T cells specific for antigens of differentiated tissue expressed extrathymically. However, these autoreactive T cells are silent in the periphery. Peripheral non-lymphoid cells (e.g., endocrine cells) can induce antigen-specific unresponsiveness in T cells and can specifically suppress production of autoantibody against their antigens when the non-lymphoid cells express class II MHC antigens on their surface. This class II MHC expression is induced by interferon-gamma produced by T cells as a result of various immune responses, such as autoimmune reaction. Thus, the expression of class II MHC antigens on non-lymphoid cells may serve as a peripheral mechanism for the induction and maintenance of self-tolerance in autoreactive T cells that escape negative selection in the thymus or that are specific for extrathymic tissue antigens, in a fail-safe mechanism against autoimmunity. Some autoimmune diseases, especially organ-specific ones, might be caused by a defect in this fail-safe mechanism.
Iwatani
Y
Y
Department of Laboratory Medicine, Osaka University Medical School, Japan.
Amino
N
N
Miyai
K
K
D001327:Autoimmune Diseases / Q000276:immunology; D015551:Autoimmunity; D004702:Endocrine Glands / Q000166:cytology / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D000949:Histocompatibility Antigens Class II