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. Overall design: Mice were fasted or fed for overnight (<12 h) and T cells purified. Ex vivo or activated T cells were subjected to epigenetic study/ transcriptomic and translatome studies. For human, blood collected in fasted condition (called as 'Pre') and again after 6 hour of having meal (called as 'Post'). Pre and post ex vivo or activated T cells subjected to transcriptome and translatome studies.