Cutting Edge: Defective Aerobic Glycolysis Defines the Distinct Effector Function in Antigen-Activated CD8+ Recent Thymic Emigrants.

Abstract

Recent thymic emigrants (RTEs) are the youngest peripheral T cells that have completed thymic selection and egress to the lymphoid periphery. RTEs are functionally distinct from their more mature but still naive T cell counterparts, because they exhibit dampened proliferation and reduced cytokine production upon activation. In this article, we show that, compared with more mature but still naive T cells, RTEs are impaired in their ability to perform aerobic glycolysis following activation. Impaired metabolism underlies the reduced IFN-γ production observed in activated RTEs. This failure to undergo Ag-induced aerobic glycolysis is caused by reduced mTORC1 activity and diminished Myc induction in RTEs. Critically, exogenous IL-2 restores Myc expression in RTEs, driving aerobic glycolysis and IFN-γ production to the level of mature T cells. These results reveal a previously unknown metabolic component to postthymic T cell maturation.