Role of TGF-Beta in the induction of Foxp3 expression and T regulatory cell function.

Introduction: 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.

Conclusions And Speculations: Generation of functional Foxp3(+) T cells via this pathway may represent a mechanism by which Treg maintain tolerance and expand their repertoire.