Transcriptome Signatures Reveal Rapid Induction of Immune-Responsive Genes in Human Memory CD8(+) T Cells.
Transcriptome Signatures Reveal Rapid Induction of Immune-Responsive Genes in Human Memory CD8(+) T Cells.
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转录组特征揭示了人类记忆 CD8( ) T 细胞中免疫反应基因的快速诱导。
DOI：
10.1038/srep27005
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发表时间：
2016-05-31
影响因子：
4.6
通讯作者：
Shen H
中科院分区：
文献类型：
--
作者：
Yang C;Khanniche A;DiSpirito JR;Ji P;Wang S;Wang Y;Shen H
记忆T细胞（TM）在保护和自身免疫中发挥着重要作用，因为它们能够比naïve T细胞（TN）产生更有效的应答。然而，TM功能增强的分子机制尚未明确，特别是在人类TM中。我们检测了刺激前后人类CD8+ TN和TM的整体基因表达谱。在刺激后0小时、4小时和24小时，TN与TM之间分别有1284、1373和1629个差异表达基因，其中TM中差异表达基因较多且表达水平较高。在TN细胞中快速上调的基因主要参与氮、核苷和氨基酸代谢。相比之下，CD8+ TM中的细胞在免疫反应相关过程中显著富集，包括细胞因子产生、淋巴细胞活化和趋化。多种细胞因子在TM细胞中迅速上调，包括已知由CD8+ T细胞产生并对其功能起重要作用的效应细胞因子，以及通常不是由CD8+ T细胞产生的促炎性和抗炎性调节细胞因子。这些结果为研究人类CD8+ TM增强功能的分子机制及其在保护和自身免疫中的突出作用提供了新的见解。
Memory T cells (TM) play a prominent role in protection and auto-immunity due to their ability to mount a more effective response than naïve T cells (TN). However, the molecular mechanisms underlying enhanced functionality of TM are not well defined, particularly in human TM. We examined the global gene expression profiles of human CD8+ TN and TM before and after stimulation. There were 1,284, 1,373 and 1,629 differentially expressed genes between TN and TM at 0 hr, 4 hr and 24 hr after stimulation, respectively, with more genes expressed to higher levels in TM. Genes rapidly up-regulated in TN cells were largely involved in nitrogen, nucleoside and amino acid metabolisms. In contrast, those in CD8+ TM were significantly enriched for immune-response-associated processes, including cytokine production, lymphocyte activation and chemotaxis. Multiple cytokines were rapidly up-regulated in TM cells, including effector cytokines known to be produced by CD8+ T cells and important for their functions, as well as regulatory cytokines, both pro- and anti-inflammatory, that are not typically produced by CD8+ T cells. These results provide new insights into molecular mechanisms that contribute to the enhanced functionality of human CD8+ TM and their prominent role in protection and auto-immunity.