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

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Abstract

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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Authors and Affiliations

  1. Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Heath, Blg. 10, Room 11N315, Bethesda, MD, 20892, USA

    Ethan M. Shevach, Todd S. Davidson, Eva N. Huter, Richard A. DiPaolo & John Andersson

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  1. Ethan M. Shevach
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  2. Todd S. Davidson
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  3. Eva N. Huter
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  4. Richard A. DiPaolo
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  5. John Andersson
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Correspondence to Ethan M. Shevach.

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Shevach, E.M., Davidson, T.S., Huter, E.N. et al. Role of TGF-β in the Induction of Foxp3 Expression and T Regulatory Cell Function. J Clin Immunol 28, 640–646 (2008). https://doi.org/10.1007/s10875-008-9240-1

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  • DOI: https://doi.org/10.1007/s10875-008-9240-1

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