Gene expression profiles of human effector CD8+ T cell subsets

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. Both subsets similarly expressed cytolytic molecules 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 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. To find the genes that potentially cause the difference in IL-2 productivity and cell survival between the CXCR1+ and CXCR1- human effector CD8+ T cell subsets, we performed microarray gene expression analysis. We highly purified each CD3+CD8+ subset for this analysis (> 95.3%) from 5 healthy individuals, and then compared the gene expression profiles of each subset.

效应性CD8+ T细胞（effector CD8+ T cells）被认为是终末分化的细胞，兼具细胞毒性活性与分泌INF-γ、TNF-α等效应细胞因子的能力。本研究针对人类CD27-CD28-效应性CD8+ T细胞的CXCR1阳性（CXCR1+）与CXCR1阴性（CXCR1-）亚群间的差异展开探究。两类亚群均相似表达溶细胞分子并展现出显著的细胞溶解活性，但仅CXCR1-亚群具备IL-2产生能力与自我增殖活性，且较CXCR1+亚群更能抵抗细胞死亡。上述差异可通过CXCR1-亚群中CAMK4、SPRY2及IL-7R的特异性上调，以及CXCR1+亚群中促凋亡基因DAPK1的上调得到解释。在CXCR1-效应性CD8+ T细胞的IL-7R阳性亚群中，IL-2产生细胞的占比高于IL-7R阴性亚群。IL-7/IL-7R信号通路仅能促进CXCR1-亚群的细胞存活。本研究揭示了一类可分泌IL-2的新型效应性CD8+ T细胞亚群，并提示该亚群在效应性CD8+ T细胞稳态维持中的重要性。为探寻可能导致CXCR1+与CXCR1-人类效应性CD8+ T细胞亚群在IL-2产生能力与细胞存活方面产生差异的基因，本研究开展了基因芯片表达谱分析。我们从5名健康个体中高度纯化得到各CD3+CD8+亚群（纯度＞95.3%），随后对各亚群的基因表达谱进行比较。