IL-7Rαlow CD8+ T Cells from Healthy Individuals Are Anergic with Defective Glycolysis

Abstract

Effector memory (EM) CD8⁺ T cells expressing lower levels of IL-7R α (IL-7Rα^low) from healthy individuals are partly compromised in vitro, but the identity of these cells has remained unclear. In this study, we demonstrate that human IL-7Rα^low EM CD8⁺ T cells are naturally occurring anergic cells in vivo and impaired in proliferation and IL-2 production but competent in IFN-γ and TNF-α production, a state that can be restored by IL-2 stimulation. IL-7Rα^low EM CD8⁺ T cells show decreased expression of GATA3 and c-MYC and are defective in metabolic reprogramming toward glycolysis, a process required for the proliferation of T cells. However, IL-7Rα^low EM CD8⁺ T cells can proliferate with TCR stimulation in the presence of IL-2 and IL-15, suggesting that these cells can be restored to normality or increased activity by inflammatory conditions and may serve as a reservoir for functional immunity.