Functional heterogeneity of human effector CD8+ T cells

Abstract

AbstractEffector CD8+ T cells are believed to be terminally differentiated cells having cytotoxic activity and the ability to produce effector cytokines such as INF-γ and TNF-α. We investigated the difference between CXCR1+ and CXCR1− subsets of human effector CD27−CD28−CD8+ T cells. The subsets expressed cytolytic molecules similarly and exerted substantial cytolytic activity, whereas only the CXCR1− subset had IL-2 productivity and self-proliferative activity and was more resistant to cell death than the CXCR1+ subset. These differences were explained by the specific up-regulation of CAMK4, SPRY2, and IL-7R in the CXCR1− subset and that of pro-apoptotic death-associated protein kinase 1 (DAPK1) in the CXCR1+ subset. The IL-2 producers were more frequently found in the IL-7R+ subset of the CXCR1− effector CD8+ T cells than in the IL-7R− subset. IL-7/IL-7R signaling promoted cell survival only in the CXCR1− subset. The present study has highlighted a novel subset of effector CD8+ T cells producing IL-2 and suggests the importance of this subset in the homeostasis of effector CD8+ T cells.