Pyruvate dehydrogenase is dispensable for T cell function in vivo

Abstract

Abstract Interrupting a major pathway in intermediary metabolism leads to an accumulation of substrates and upstream metabolites, downstream product deficiency, changes in feedback inhibition or activation, and diversion to alternative pathways. All of which may compromise cellular function. T cells are highly dependent upon metabolic reprogramming for activation and differentiation, suggesting that complete disruption of a major metabolic node like pyruvate dehydrogenase complex (PDC) will affect immunity. Here we show that genetic ablation of PDC activity in T cells leads to significant disruptions of glycolysis, the tricarboxylic acid cycle and oxidative phosphorylation. Despite perturbations in these major metabolic pathways, antiviral adaptive immunity is preserved in vivo. This preservation of function is likely due to the provision of necessary metabolites by the immune environment in vivo. Overall, our data indicate that PDC is dispensable for T cell function in vivo.