Chemical individuality in T cells: A Garrodian view of immunometabolism

Abstract Metabolically quiescent T cells circulate throughout the body in search of antigen. Following engagement of their cognate receptors, T cells undergo metabolic reprogramming to support their activation, differentiation, and ultimately function. In the spirit of Sir Archibald Garrod, this metabolic reprogramming actually imparts a chemical individuality which confers advantage, while in others confers vulnerability, depending upon the milieu. Studying T cell immunometabolism in the context of inborn errors of metabolism allows one to define essential pathways of intermediary metabolism as well metabolic vulnerabilities and plasticity. Inborn errors of metabolism, a class of diseases first named by Garrod, have a long history of being informative for common physiologic and pathologic processes. This endeavor may be accomplished through the study of patients, animal models, and in vitro models of inborn errors of metabolism. In this review, the basics of intermediary metabolism and core metabolic pathways will be discussed, along with their relationship to T cell immunometabolism. Due to their pleiotropic nature, the reader will be specifically directed toward various inborn errors of metabolism which may be helpful for answering important questions about the role of metabolism in T cells.