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

EM Shevach, TS Davidson, EN Huter… - Journal of clinical …, 2008 - Springer
EM Shevach, TS Davidson, EN Huter, RA DiPaolo, J Andersson
Journal of clinical immunology, 2008Springer
Introduction 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 …
Introduction
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.
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