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Updated: Jun 30, 2026

In Vitro Differentiation of Human CD4+FOXP3+ Induced Regulatory T Cells (iTregs) from Naïve CD4+ T Cells Using a TGF-β-containing Protocol
Published on: December 30, 2016
Role of TGF-Beta in the induction of Foxp3 expression and T regulatory cell function
Ethan M Shevach1, Todd S Davidson, Eva N Huter
1Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Heath, Blg. 10, Room 11N315, Bethesda, MD 20892, USA. eshevach@niaid.nih.gov
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.
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