Cutting Edge: Glycolytic Metabolism and Mitochondrial Metabolism Are Uncoupled in Antigen-Activated CD8⁺ Recent...

Recent thymic emigrants (RTEs) are peripheral T cells that have most recently completed selection and thymic egress and constitute a population that is phenotypically and functionally distinct from its more mature counterpart. Ag-activated RTEs are less potent effectors than are activated mature T cells, due in part to reduced aerobic glycolysis (correctable by exogenous IL-2), which in turn impacts IFN-γ production. Mitochondria serve as nodal regulators of cell function, but their contribution to the unique biology of RTEs is unknown. In this study, we show that activated mouse RTEs have impaired oxidative phosphorylation, even in the presence of exogenous IL-2. This altered respiratory phenotype is the result of decreased CD28 signaling, reduced glutaminase induction, and diminished mitochondrial mass in RTEs relative to mature T cells. These results suggest an uncoupling whereby IL-2 tunes the rate of RTE glycolytic metabolism, whereas the unique profile of RTE mitochondrial metabolism is "hard wired."