Postprandial changes to systemic metabolism imprint durable changes to T cell immunity [ATAC-seq]

Systemic nutrient availability waxes and wanes with dietary input. Here we show that short periods of fasting and refeeding have long-lasting effects on T cell immunity. Human or murine T cells from fed hosts have higher metabolic capacity than those from fasted hosts ex vivo and show better/superior metabolic phenotype and immune response/functions in vitro and in vivo settings of virus infection or tumor model. Serum or chylomicrons enriched from lymphatics of fed mice restores the metabolic and immune functions of fasted T cells. Fed T cells had heightened mTORC1-dependent translation of key immunologic and metabolic genes independent of their epigenetic and transcriptional status. mTORC1 inhibition during the fed period mitigates the postprandial benefit of fed T cells over fasted cells. Our data highlight the need to consider diet content and timing as key factors in immune cell analysis, vaccination strategies, and the generation of cellular therapies.