Mitochondrial Priming By CD28

Abstract

CD28 costimulation ensures full T cell activation, promoting glycolytic flux needed for effector T (T_E) cell differentiation and proliferation. T cell receptor (TCR) signalling in the absence of costimulation can elicit primary T_E cell responses, but the memory T (T_M) cells generated during this process are anergic, failing to respond to secondary antigen exposure. While much is known about how CD28 regulates glycolysis, little is understood about how it contributes to the generation of long-lived T_M cells, which are metabolically characterized by their reliance on fatty acid oxidation (FAO), fused mitochondria with tight cristae, and spare respiratory capacity. CD28 is a target of current and developing immunotherapies, so understanding how it regulates T cell function is of broad interest and clinical importance. Our results show that initial CD28 signals during T cell activation prime mitochondria with latent metabolic capacity essential for future T cell responses. How costimulatory signals during activation influence T cell metabolism and function will be discussed.