Kumar Ar, Dayana B. Rivadeneira, Isha Mehta, Bingxian Xie, Rachel Cumberland, Supriya Joshi, Jitendra S. Kanshana, William G. Gunn, Victoria Dean, Angelina Parise, Kristin Morder, Erica S. Myers, Steven J. Mullett, Richard Cattley, Stacy L Gelhaus, Abigail E. Overacre-Delgoffe, Jishnu Das, William F. Hawse, Alison B. Kohan, Greg M. Delgoffe
Although intrinsic metabolic pathways have critical roles in T cell function1,2, 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. Experiments in mice and humans show enhancement of T cell function following fasting and refeeding, caused by persistent immunometabolic reprogramming, with potential implications for nutritional interventions and adoptive cell therapy.