Role of TGF-Beta in the induction of Foxp3 expression and T regulatory cell function.
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.
Shevach
Ethan M
EM
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
Davidson
Todd S
TS
Huter
Eva N
EN
Dipaolo
Richard A
RA
Andersson
John
J
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*
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007376:Interleukin-2; D016212:Transforming Growth Factor beta