Nutrient allocation fuels T cell-mediated immunity

T cell activation and function are intricately linked to metabolic reprogramming. The classic view of T cell metabolic reprogramming centers on glucose as the dominant bioenergetic fuel, where T cell receptor (TCR) stimulation promotes a metabolic switch from relying primarily on oxidative phosphorylation (OXPHOS) for energy production to aerobic glycolysis (i.e., the Warburg effect). More recently, studies have revealed this classic model to be overly simplistic. Activated T cells run both glycolysis and OXPHOS programs concurrently, allocating diverse nutrient sources toward distinct biosynthetic and bioenergetic fates. Moreover, studies of T cell metabolism in vivo and ex vivo highlight that physiologic nutrient availability influences how glucose is allocated by T cells to fuel both optimal proliferation and effector function. Here, we summarize recent advancements that support a revised model of effector T cell metabolism, where strategic nutrient allocation fuels optimal T cell-mediated immunity. Glucose has traditionally been considered the primary fuel for T cells. Longo et al. present evidence for a revised, “nutrient allocation” model, in which effector T cells channel diverse nutrient sources into specific metabolic pathways to fuel T cell-mediated immunity.