Signal transduction in CD4+CD25+ regulatory T cells: CD25 and IL-2.
IL-2 was originally identified as a growth factor critical for T cell proliferation in vitro. Although the early studies of IL-2 strongly implied an obligate role of IL-2 in T cell growth, it was later shown that mice deficient in IL-2 or in IL-2R developed an unexpected lymphocytic hyperproliferation and subsequent autoimmune disease. In separate studies of autoimmunity, it was observed that a population of CD4+ T cells suppressed the induction of autoimmunity in several in vivo models of autoimmune disease. It was not until the characterization of this subpopulation of CD4+ T cells demonstrated that they co-expressed the IL-2R-alpha chain (CD25) that the puzzling phenotype observed in IL-2 deficient mice began to be truly explained. The constitutive expression of the IL-2R-alpha chain on CD4+CD25+ T cells led to the obvious speculation that IL-2 signaling in CD4+CD25+ T cells was important to these cells. Recent studies have examined the role of IL-2 in the generation, the expansion, the survival and the effector function of CD4+CD25+ T cells. It is now evident that IL-2 is critical for the development of CD4+CD25+ T cells and the phenotype observed in IL-2 and IL-2R deficient mice is most readily explained by the absence of these potent suppressors.
Thornton
Angela M
AM
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. athornton@niaid.nih.gov
D000818:Animals; D015551:Autoimmunity; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007107:Immune System; D007108:Immune Tolerance; D007376:Interleukin-2 / Q000378:metabolism*; D008214:Lymphocytes / Q000166:cytology; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D010641:Phenotype; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*; D019076:Transgenes
D016207:Cytokines; D007376:Interleukin-2; D015375:Receptors, Interleukin-2