Metabolism of activated T lymphocytes

Abstract

Activated T cells undergo metabolic reprogramming which promotes glycolytic flux and lactate production as well as elevated production of lipids, proteins, nucleic acids and other carbohydrates (i.e. induction of biomass) even in the presence of oxygen. Activated T cells show induced expression of, among other things, Glucose Transporter 1 and several glycolytic enzymes, including ADP-Dependent Glucokinase and the low affinity isoform Pyruvate Kinase-M2 (which promote glycolytic flux), as well Glutamine Transporters and Glycerol-3-phosphate Dehydrogenase 2 which make available glutamate and glycerol-3-phosphate as mitochondrial energy sources. Intracellular leucine concentrations critically regulate mammalian target of rapamycin (mTOR) signaling to promote Th1, Th2, and Th17 CD4(+) T effector cell differentiation. In contrast, T regulatory (Treg) cells are generated when AMP-Activating Protein Kinase signaling is activated and mTOR activation is suppressed. Unlike effector CD4(+) and CD8(+) T cells, Tregs and memory T cells oxidize fatty acids for fuel. Effector and memory T cells perform different functions and thus show distinct metabolic profiles which are exquisitely controlled by cellular signaling. Upon activation, T cells express the insulin and leptin receptors on their surface and become sensitive to insulin signaling and nutrient availability and show changes in differentiation. Thus, metabolism and nutrient availability influence T cell activation and function.