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.