Journal of Clinical Immunology

, Volume 28, Issue 6, pp 640–646

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

  • Ethan M. Shevach
  • Todd S. Davidson
  • Eva N. Huter
  • Richard A. DiPaolo
  • John Andersson
Article

DOI: 10.1007/s10875-008-9240-1

Cite this article as:
Shevach, E.M., Davidson, T.S., Huter, E.N. et al. J Clin Immunol (2008) 28: 640. doi:10.1007/s10875-008-9240-1

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.

Keywords

TGF-βgastritisinfectious toleranceimmune suppressionlatency-associated peptide

Copyright information

© Springer Science + Business Media, LLC 2008

Authors and Affiliations

  • Ethan M. Shevach
    • 1
  • Todd S. Davidson
    • 1
  • Eva N. Huter
    • 1
  • Richard A. DiPaolo
    • 1
  • John Andersson
    • 1
  1. 1.Laboratory of ImmunologyNational Institute of Allergy and Infectious Diseases, National Institutes of HeathBethesdaUSA