, Volume 28, Issue 6, pp 640-646
Date: 23 Sep 2008

Role of TGF-β in the Induction of Foxp3 Expression and T Regulatory Cell Function

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A number of studies have suggested that transforming growth factor beta (TGF-β) plays a critical role in immune suppression mediated by Foxp3+ regulatory T cells. TGF-β in concert with interleukin 2 is a potent induction factor for the differentiation of Foxp3+ Treg from naive precursors. Polyclonal TGF-β-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-β 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-β-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.