Metabolic regulation of T lymphocytes

Abstract

T cell activation leads to dramatic shifts in cell metabolism to protect against pathogens and to orchestrate the action of other immune cells. Quiescent T cells require predominantly ATP-generating processes, whereas proliferating effector T cells require high metabolic flux through growth-promoting pathways. Further, functionally distinct T cell subsets require distinct energetic and biosynthetic pathways to support their specific functional needs. Pathways that control immune cell function and metabolism are intimately linked, and changes in cell metabolism at both the cell and system levels have been shown to enhance or suppress specific T cell functions. As a result of these findings, cell metabolism is now appreciated as a key regulator of T cell function specification and fate. This review discusses the role of cellular metabolism in T cell development, activation, differentiation, and function to highlight the clinical relevance and opportunities for therapeutic interventions that may be used to disrupt immune pathogenesis.

Figure 1

T cell metabolic programs match functional demands. Resting T cells oxidize glucose-derived pyruvate, along with lipids and amino acids, to efficiently produce ATP/energy required for immune surveillance. Upon activation, lipid oxidation is downregulated, and glycolysis increases along with glutamine oxidation, in order to produce biosynthetic precursors required for rapid cell growth and proliferation. At the end of an immune response, the cells that survive to become memory T cells revert back to lipid oxidation with increased capacity for efficient energy generation.

Figure 2

Specific T cell lineages possess unique metabolic profiles that are essential for their function and maintenance. The predominant metabolic program and key regulators are highlighted for each of the T cell subtypes shown here.