Distinct metabolic programs control the effector fate of γδ T cell subsets and their activities in the tumour microenvironment

Metabolic programming controls immune cell lineages and functions, but little is known about γδ T cell metabolism. Here we found that γδ T cell subsets making either IFN-γ or IL-17 have intrinsically distinct metabolic requirements. Whereas IFN-γ+ γδ T cells were almost exclusively dependent on glycolysis, IL-17+ γδ T cells strongly engaged oxidative metabolism, with increased mitochondrial mass and activity. These distinct metabolic signatures were surprisingly imprinted early during γδ thymic development, and were stably maintained in the periphery and within tumours. Tetramethylrhodamine, ethyl ester (TMRE)-labelled γδ T cells, from fetal C57BL/6 thymic lobes cultured for 2 days, were sorted into TMREhi and TMRElo CD24+ γδ T cells.