Functional heterogeneity of human effector CD8⁺ T cells

Effector 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.