Regulatory Role Of Vγ1γδT Cells In Tumor Immunity

It has been demonstrated that Vγ1γδ T cells and Vγ4γδ T cells, the twomain subsets of peripheral γδ T cells, have different functions in manydiseases. In our previous report, we showed that Vγ4γδ T cells exerteda protective role in tumor immune responses througheomesodermin-controlled mechanisms when transferred into TCR δ-/-mice. However, the precise roles of Vγ1γδ T cells in tumor immunity,especially whether Vγ1γδ T cells and Vγ4γδ T cells interact with eachother, are unknown. We demonstrated in this study that Vγ1γδ T cellssuppressed Vγ4γδ T cell-mediated antitumor immunity in vitro and invivo, and this suppression was cell contact independent. Usinganti–IL-4neutralizing antibody or IL-4knockout mice, we determined the suppressive molecule derived from Vγ1γδ T cells was IL-4.Treatment of in vitro expanded Vγ4γδ T cells with recombinant IL-4significantly reduced expression of NKG2D, Perforin, and IFN-γ.Finally, under Th2priming condition, Vγ1γδ T cells produced higherlevel of GATA-3in comparison with Vγ4γδ T cells. Therefore, ourresults established for the first time a negative regulatory role of Vγ1γδ Tcells in antitumor immunity through cell contact-independent andIL-4–mediated suppression on Vγ4γδ T cells. Selective inactivation ofthis suppressive Vγ1γδ T cells may be beneficial for tumor immunetherapy.