The Ups and Downs of Metabolism during the Lifespan of a T Cell

Understanding the various mechanisms that govern the development, activation, differentiation, and functions of T cells is crucial as it could provide opportunities for therapeutic interventions to disrupt immune pathogenesis. Immunometabolism is one such area that has garnered significant interest in the recent past as it has become apparent that cellular metabolism is highly dynamic and has a tremendous impact on the ability of T cells to grow, activate, and differentiate. In each phase of the lifespan of a T-cell, cellular metabolism has to be tailored to match the specific functional requirements of that phase. Resting T cells rely on energy-efficient oxidative metabolism but rapidly shift to a highly glycolytic metabolism upon activation in order to meet the bioenergetically demanding process of growth and proliferation. However, upon antigen clearance, T cells return to a more quiescent oxidative metabolism to support T cell memory generation. In addition, each helper T cell subset engages distinct metabolic pathways to support their functional needs. In this review, we provide an overview of the metabolic changes that occur during the lifespan of a T cell and discuss several important studies that provide insights into the regulation of the metabolic landscape of T cells and how they impact T cell development and function.