Gonçalves-Sousa, NatachaRibot, Julie C.Barros, Ana deCorreia, Daniel V.Caramalho, ÍrisSilva-Santos, Bruno2012-11-062012-11-062010Eur. J. Immunol. 2010. 40: 61–700014-2980http://dx.doi.org/10.1002/eji.200939715http://hdl.handle.net/10451/7172http://onlinelibrary.wiley.com/doi/10.1002/eji.200939715/pdf© 2010 WILEYγδ T cells are highly cytolytic lymphocytes that produce large amounts of pro-inflammatory cytokines during immune responses to multiple pathogens. Furthermore, their ability to kill tumor cells has fueled the development of γδ-T-cell-based cancer therapies. Thus, the regulation of γδ-T-cell activity is of great biological and clinical relevance. Here, we show that murine CD4+CD25+ αβ T cells, the vast majority of which express the Treg marker, Foxp3, abolish key effector functions of γδ T cells, namely the production of the pro-inflammatory cytokines, IFN-γ and IL-17, cytotoxicity, and lymphocyte proliferation in vitro and in vivo. We further show that suppression is dependent on cellular contact between Treg and γδ T cells, results in the induction of an anergic state in γδ lymphocytes, and can be partially reversed by manipulating glucocorticoid-induced TNF receptor-related protein (GITR) signals. Our data collectively dissect a novel mechanism by which the expansion and pro-inflammatory functions of γδ T cells are regulated.engγδ T cellsIFN-γIL-17TregT-cell suppressionjournal article