title: Role of TGF-Beta in the induction of Foxp3 expression and T regulatory cell function.
abstract: BACKGROUND
  A number of studies have suggested that transforming growth factor beta (TGF-beta) plays a critical role in immune suppression mediated by Foxp3(+) regulatory T cells. TGF-beta in concert with interleukin 2 is a potent induction factor for the differentiation of Foxp3(+) Treg from naive precursors. Polyclonal TGF-beta-induced Treg (iTreg) are capable of preventing the autoimmune syndrome that develops in scurfy mice that lack Foxp3(+) Treg. Antigen-specific iTreg can be used to both prevent and treat autoimmune gastritis that is induced by transfer of naive or primed autoantigen-specific T cells. TGF-beta complexed with latency-associated peptide is expressed on the surface of activated thymus-derived Treg. Coculture of activated Treg with naive responder T cells results in the de novo generation of fully functional Foxp3(+) T cells in a contact-dependent and TGF-beta-dependent manner.
  Generation of functional Foxp3(+) T cells via this pathway may represent a mechanism by which Treg maintain tolerance and expand their repertoire.
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Heath, Blg. 10, Room 11N315, Bethesda, MD 20892, USA. eshevach@niaid.nih.gov
authors.forename: Ethan M
authors.initials: EM
authors.lastname: Shevach
authors.forename: Todd S
authors.initials: TS
authors.lastname: Davidson
authors.forename: Eva N
authors.initials: EN
authors.lastname: Huter
authors.forename: Richard A
authors.initials: RA
authors.lastname: Dipaolo
authors.forename: John
authors.initials: J
authors.lastname: Andersson
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000096:biosynthesis*; D007108:Immune Tolerance / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology*
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007376:Interleukin-2; D016212:Transforming Growth Factor beta