T lymphocyte-mediated control of autoimmunity.
Autoreactive T cells can be readily identified in the peripheral lymphocyte pool of both humans and experimental animals. Peripheral tolerance may be maintained by regulatory/suppressor T cells which prevent the activation of autoantigen-specific cells. Mice thymectomized on day 3 of life (d3Tx) develop a wide spectrum of organ-specific autoimmune diseases. Reconstitution of d3Tx mice with CD4+ CD25+ T cells from normal mice prevents the development of disease. Similarly, CD4+ CD25+ T cells prevent the transfer of disease by autoantigen-specific cloned T cells derived from d3Tx mice. Thus, regulatory T cells can prevent both the induction and effector function of autoreactive T cells. In vitro, the CD4+ CD25+ population is anergic to stimulation through the T cell receptor (TCR) and suppresses the proliferative responses of normal CD4+ CD25- cells by a contract-dependent mechanism. Suppression is not MHC-dependent, but requires activation of the CD4+ CD25+ population. The mechanism of suppression in vivo and the target antigen(s) of this unique regulatory population remain to be characterized.
Shevach
E M
EM
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Thornton
A
A
Suri-Payer
E
E
D019264:Adoptive Transfer; D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology; D015551:Autoimmunity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019070:Cell Lineage; D017635:Clonal Anergy; D007108:Immune Tolerance; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013934:Thymectomy
D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2