Role of gd T Cells in a-Galactosylceramide-Mediated Immunity

study, we showed that gd T cells, another population of innate-like T lymphocytes, displayed a phenotype of activated cells (cytokine production and cytotoxic properties) and were required to achieve an optimal a-GalCer–induced immune response. Using gene-targeted mice and recombinant cytokines, a critical need for IL-12 and IL-18 has been shown in the a-GalCer–induced IFN-g production by gd T cells. Moreover, this cytokine production occurred downstream of type I NKT cell response, suggesting their bystander effect on gd T cells. In line with this, gd T cells failed to directly recognize the CD1d/a-GalCer complex. We also provided evidence that gd T cells increase their cytotoxic properties after a-GalCer injection, resulting in an increase in killing of tumor cell targets. Moreover, using cancer models, we demonstrated that gd T cells were required for an optimal a-GalCer– mediated anti-tumor activity. Finally, we reported that immunization of wild-type mice with a-GalCer enhanced the adaptive immune response elicited by OVA, and this effect was strongly mediated by gd T cells. We conclude that gd T cells amplify the innate and acquired response to a-GalCer, with possibly important outcomes for the therapeutic effects of this compound. The Journal of Immunology, 2012, 188: 000–000.