title: γδ T cells restrain extrathymic development of Foxp3+-inducible regulatory T cells via IFN-γ.
abstract: Inducible Treg (iTreg) cells generated from Ag-stimulated naïve CD4(+) T cells in the periphery play an important role in regulating immune responses. TGF-β is a key cytokine that promotes this conversion process; however, how this process is regulated in vivo remains unclear. Here, we report that γδ T cells play a crucial role in controlling iTreg generation and suppressor function. Ag-induced iTreg generation was significantly enhanced in C57BL/6 mice in the absence of γδ T cells. Inhibition of iTreg conversion was mediated by IFN-γ produced by activated γδ T cells but not by activated CD4(+) T cells. BM chimera experiments further confirmed γδ-derived IFN-γ-dependent mechanism in regulating iTreg generation in vivo. Lastly, human peripheral blood γδ T cells also interfere with iTreg conversion via IFN-γ. Our results suggest a novel function of γδ T cells in limiting the generation of iTreg cells, potentially balancing immunity and tolerance.
authors.affiliation: Department of Immunology, Lerner Research Institute, Cleveland, OH, USA; Department of Molecular Medicine, Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Anabelle
authors.initials: A
authors.lastname: Visperas
authors.forename: Bo
authors.initials: B
authors.lastname: Shen
authors.forename: Booki
authors.initials: B
authors.lastname: Min
mesh_terms: D000818:Animals; D051858:Forkhead Transcription Factors / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D051858:Forkhead Transcription Factors; D007371:Interferon-gamma
keywords: CD4+ T cell; IFN-γ; Inflammation; Intestine; Oral tolerance; Regulatory T cells; iTreg cells; γδ T cell