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.
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
E M
EM
Shevach
A
A
Thornton
E
E
Suri-Payer
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