Metabolic orchestration of T lineage differentiation and function.

T cells are stimulated by the engagement of antigen, cytokine, pathogen, and hormone receptors. While research performed over many years has focused on deciphering the molecular components of these pathways, recent data underscore the importance of the metabolic environment in conditioning responses to receptor engagement. The ability of T cells to undergo a massive proliferation and cytokine secretion in response to receptor signals requires alterations to their bioenergetic homeostasis, allowing them to meet new energetic and biosynthetic demands. The metabolic reprogramming of activated T cells is regulated not only by changes in intracellular nutrient uptake and utilization but also by nutrient and oxygen concentrations in the extracellular environment. Notably, the extracellular environment can be profoundly altered by pathological conditions such as infections and tumors, thereby perturbing the metabolism and function of antigen-specific T lymphocytes. This review highlights the interplay between diverse metabolic networks and the transcriptional/epigenetic states that condition T-cell differentiation, comparing the metabolic features of T lymphocytes with other immune cells. We further address recent discoveries in the metabolic pathways that govern T-cell function in physiological and pathological conditions.