Postprandial lipid metabolism durably enhances T cell immunity.

, systemic nutrient availability is in constant flux. Yet, how postprandial metabolism affects T cell fate has been less studied. Here we show that the short-term nutritional state of an individual has marked effects on T cell immunity. Human or murine T cells from fed hosts had higher metabolic capacity than those from fasted hosts, and this increase in capacity persisted after activation and expansion in vitro or in vivo. Triglyceride-rich chylomicrons in serum were drivers of postprandial immunometabolic reprogramming, and chylomicrons primed mTORC1-dependent translation ex vivo and after activation, which markedly enhanced effector function after priming. Human postprandial CAR-T cells manufactured from the same donor showed a therapeutic advantage over T cells collected while individuals were fasted. Thus, postprandial metabolism imparts durable metabolic and functional advantages to T cells, highlighting the importance of considering nutritional status in immunological analysis, vaccination and generation of cellular therapies.