gamma[deltaT cells restrain extrathymic development of Foxp3+-inducible regulatory T cells via IFN-[gamma

• Published in: European journal of immunology Vol. 44; no. 8; p. 2448
• Main Authors: Visperas, Anabelle, Shen, Bo, Min, Booki
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 01.08.2014
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201344331

Inducible Treg (iTreg) cells generated from Ag-stimulated naïve CD4+ T cells in the periphery play an important role in regulating immune responses. TGF-[beta] is a key cytokine that promotes this conversion process; however, how this process is regulated in vivo remains unclear. Here, we report that [gamma][delta] 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 [gamma][delta] T cells. Inhibition of iTreg conversion was mediated by IFN-[gamma] produced by activated [gamma][delta] T cells but not by activated CD4+ T cells. BM chimera experiments further confirmed [gamma][delta]-derived IFN-[gamma]-dependent mechanism in regulating iTreg generation in vivo. Lastly, human peripheral blood [gamma][delta] T cells also interfere with iTreg conversion via IFN-[gamma]. Our results suggest a novel function of [gamma][delta] T cells in limiting the generation of iTreg cells, potentially balancing immunity and tolerance. [PUBLICATION ABSTRACT]