γδ T Cells Provide an Early Source of Interferon γ in Tumor Immunity

Interferon (IFN)-gamma is necessary for tumor immunity, however, its initial cellular source is unknown. Because gammadelta T cells primarily produce this cytokine upon activation, we hypothesized that they would provide an important early source of IFN-gamma in tumor immunosurveillance. To address this hypothesis, we first demonstrated that gammadelta T cell-deficient mice had a significantly higher incidence of tumor development after challenge with a chemical carcinogen methylcholanthrene (MCA) or inoculation with the melanoma cell line B16. In wild-type mice, gammadelta T cells were recruited to the site of tumor as early as day 3 after inoculation, followed by alphabeta T cells at day 5. We then used bone marrow chimeras and fetal liver reconstitutions to create mice with an intact gammadelta T cell repertoire but one that was specifically deficient in the capacity to produce IFN-gamma. Such mice had a higher incidence of tumor development, induced either with MCA or by inoculation of B16 melanoma cells, compared with mice with IFN-gamma-competent gammadelta T cells. Moreover, genetic deficiency of gammadelta T cells resulted in impaired IFN-gamma production by tumor antigen-triggered alphabeta T cell upon immunization with tumor lysate. These results demonstrate that gammadelta T cells can play a necessary role in tumor immunity through provision of an early source of IFN-gamma that in turn may regulate the function of tumor-triggered alphabeta T cells.