Center for AIDS Research, Kumamoto University, Kumamoto, Japan.
Blood. 2012 Feb 9;119(6):1390-8. doi: 10.1182/blood-2011-03-343251. Epub 2011 Dec 14.
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.
效应性 CD8(+) T 细胞被认为是终末分化细胞，具有细胞毒性活性和产生效应细胞因子（如 INF-γ 和 TNF-α）的能力。我们研究了人类效应性 CD27(-)CD28(-)CD8(+) T 细胞中 CXCR1(+)和 CXCR1(-)亚群之间的差异。这两个亚群表达的细胞溶解分子相似，并发挥了实质性的细胞溶解活性，而只有 CXCR1(-)亚群具有 IL-2 产生能力和自我增殖活性，并且比 CXCR1(+)亚群更能抵抗细胞死亡。这些差异可以通过 CXCR1(-)亚群中特定上调 CAMK4、SPRY2 和 IL-7R，以及 CXCR1(+)亚群中上调促凋亡死亡相关蛋白激酶 1（DAPK1）来解释。在 CXCR1(-)效应性 CD8(+) T 细胞的 IL-7R(+)亚群中，IL-2 产生细胞比在 IL-7R(-)亚群中更为常见。IL-7/IL-7R 信号仅在 CXCR1(-)亚群中促进细胞存活。本研究突出了一种新型的产生 IL-2 的效应性 CD8(+) T 细胞亚群，并提示该亚群在效应性 CD8(+) T 细胞的体内平衡中具有重要意义。
