Regulators of Glucose Metabolism in CD4+ and CD8+ T Cells

Abstract

Much like cancer cells, activated T cells undergo various metabolic changes that allow them to grow and proliferate rapidly. By adopting aerobic glycolysis upon activation, T cells effectively prioritize efficiency in biosynthesis over energy generation. There are distinct differences in the way CD4⁺ and CD8⁺ T cells process activation signals. CD8⁺ effector T cells are less dependent on Glut1 and oxygen levels compared to their CD4⁺ counterparts. Similarly the downstream signaling by TCR also differs in both effector T cell types. Recent studies have explored PI3K/Akt, mTORC, HIF1α, p70S6K and Bcl-6 signaling in depth providing definition of the crucial roles of these regulators in glucose metabolism. These new insights may allow improved therapeutic manipulation against inflammatory conditions that are associated with dysfunctional T-cell metabolism such as autoimmune disorders, metabolic syndrome, HIV, and cancers.

Keywords: Akt; Bcl-6; Glut1; HIF1α; PDK-1; PI3K; T cells; T-cell activation; glucose; mTORC.