Self/nonself discrimination among immunoregulatory (CD4) T cells.
This review covers work on immunological tolerance from 1962 up to the present, focusing on the Th, CD4+ compartment of the immune system. The principle mechanism of tolerance is identified as deletion, occurring centrally and in the periphery. In the periphery, deletion is the normal response of CD4 T cells to soluble monomeric proteins that occurs when activation (mainly of dendritic cells) is avoided. Thus activation and the signals which induce it are crucial to understanding S/NS discrimination, as has long been known. The thymus is important as the site where new T cells first see self-antigens, and as one largely shielded from activation, although deletion in the thymus and the periphery has the same threshold. The relative contribution of dendritic cells and developing T cells to deletion in the thymus remains unclear. Activation induced cell death, containment, anergy and deviation constitute subsidiary mechanisms, and sequestration/neglect is important in limiting the scope of deletion.
Department of Immunology, Windeyer Institute of Medical Sciences, 46 Cleveland Street, London, W1P 6DB. n.mitchison@ucl.ac.uk
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D000818:Animals; D000941:Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D017637:Clonal Deletion; D049673:History, 20th Century; D008208:Lymphatic System / Q000276:immunology; D017634:Self Tolerance / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology
D000941:Antigens