Cutting Edge: IL-2 is essential for TGF-beta-mediated induction of Foxp3+ T regulatory cells.
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.
Davidson
Todd S
TS
Cellular Immunology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
DiPaolo
Richard J
RJ
Andersson
John
J
Shevach
Ethan M
EM
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
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