Il-7ralow cd8+ t cells from healthy individuals are anergic with defective glycolysis

Effector memory (EM) CD8+ T cells expressing lower levels of IL-7R a (IL-7Ralow) 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-7Ralow EM CD8+ T cells are naturally occurring anergic cells in vivo and impaired in proliferation and IL-2 production but competent in IFN-g and TNF-a production, a state that can be restored by IL-2 stimulation. IL-7Ralow 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-7Ralow 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.