title: Cutting Edge: IL-2 is essential for TGF-beta-mediated induction of Foxp3+ T regulatory cells.
abstract: TGF-beta is a pluripotent cytokine that is capable of inducing the expression of Foxp3 in naive T lymphocytes. TGF-beta-induced cells are phenotypically similar to thymic-derived regulatory T cells in that they are anergic and suppressive. We have examined the cytokine and costimulatory molecule requirements for TGF-beta-mediated induction and maintenance of Foxp3 by CD4(+)Foxp3(-) cells. IL-2 plays a non-redundant role in TGF-beta-induced Foxp3 expression. Other common gamma-chain-utilizing cytokines were unable to induce Foxp3 expression in IL-2-deficient T cells. The role of CD28 in the induction of Foxp3 was solely related to its capacity to enhance the endogenous production of IL-2. Foxp3 expression was stable in vitro and in vivo in the absence of IL-2. As TGF-beta-induced T regulatory cells can be easily grown in vitro, they may prove useful for the treatment of autoimmune diseases, for the prevention of graft rejection, and graft versus host disease.
authors: Cellular Immunology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Todd S
authors: TS
authors: Davidson
authors: Richard J
authors: RJ
authors: DiPaolo
authors: John
authors: J
authors: Andersson
authors: Ethan M
authors: EM
authors: Shevach
mesh_terms: D000818:Animals; D018106:CD28 Antigens / Q000502:physiology; D015704:CD4 Antigens / Q000032:analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D051379:Mice; D008822:Mice, Transgenic; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D018106:CD28 Antigens; D015704:CD4 Antigens; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; C499308:Rag2 protein, mouse; D016212:Transforming Growth Factor beta