Sugar, fat, and protein: new insights into what T cells crave

Abstract

T cell activation and differentiation is a complex process that has evolved beyond the two-signal model to a number of varied and opposing inputs that must be interpreted to make a cell fate decision. While stimulation through the TCR, costimulatory, and cytokine receptors is required, metabolic signaling has emerged not only as an activation signal, but also one that can influence and shape differentiation. Recent findings have revealed unappreciated roles for glucose, fatty acids, and salt in the function of many T cell subsets. In this review, we will highlight the latest advances in the burgeoning field of immunometabolism, focusing on how the menu of T cell fuels has expanded.

Figure 1. T cells dramatically shift metabolism when in their effector phase

During T cell expansion, glucose is preferentially fermented into lactic acid, while other metabolites are used to generate intermediates required for cellular growth and proliferation (left). In periods of quiescence, T cells utilize glucose, amino acids, and fatty acids (intrinsic or extrinsic) in order to generate ATP via oxidative phosphorylation (right). While effector cells activate oxidative phosphorylation during T cell activation, aerobic glycolysis is required for optimal effector cell function and cytokine secretion.