Department of Immunology, Laboratory for Medical Immunology, Erasmus MC, Rotterdam, 3000 CA, The Netherlands.
Department of Rheumatology, University Medical Centre Groningen, Groningen, 9700 RB, The Netherlands.
Sci Rep. 2017 Jul 14;7(1):5509. doi: 10.1038/s41598-017-05849-1.
Ageing is a broad cellular process, largely affecting the immune system, especially T-lymphocytes. Additionally to immunosenescence alone, cytomegalovirus (CMV) infection is thought to have major impacts on T-cell subset composition and exhaustion. These impacts have been studied extensively in TCRαβ+ T-cells, with reduction in naive, increase in effector (memory) subsets and shifts in CD4/CD8-ratios, in conjunction with morbidity and mortality in elderly. Effects of both ageing and CMV on the TCRγδ+ T-cell compartment remain largely elusive. In the current study we investigated Vγ- and Vδ-usage, maturation, differentiation and exhaustion marker profiles of both CD4 and CD8 double-negative (DN) and CD8+TCRγδ+ T-cells in 157 individuals, age range 20-95. We observed a progressive decrease in absolute numbers of total TCRγδ+ T-cells in blood, affecting the predominant Vγ9/Vδ2 population. Aged TCRγδ+ T-cells appeared to shift from naive to more (late-stage) effector phenotypes, which appeared more prominent in case of persistent CMV infections. In addition, we found effects of both ageing and CMV on the absolute counts of exhausted TCRγδ+ T-cells. Collectively, our data show a clear impact of ageing and CMV persistence on DN and CD8+TCRγδ+ T-cells, similar to what has been reported in CD8+TCRαβ+ T-cells, indicating that they undergo similar ageing processes.
衰老是一个广泛的细胞过程，主要影响免疫系统，特别是 T 淋巴细胞。除了免疫衰老本身，巨细胞病毒 (CMV) 感染被认为对 T 细胞亚群组成和衰竭有重大影响。这些影响在 TCRαβ+T 细胞中得到了广泛研究，幼稚细胞减少，效应（记忆）亚群增加，CD4/CD8 比值发生变化，同时老年患者发病率和死亡率增加。衰老和 CMV 对 TCRγδ+T 细胞区室的影响在很大程度上仍不清楚。在本研究中，我们研究了 157 名年龄在 20-95 岁的个体中 CD4 和 CD8 双阴性 (DN) 和 CD8+TCRγδ+T 细胞的 Vγ-和 Vδ-使用、成熟、分化和衰竭标志物谱。我们观察到血液中总 TCRγδ+T 细胞的绝对数量逐渐减少，这影响了主要的 Vγ9/Vδ2 群体。衰老的 TCRγδ+T 细胞似乎从幼稚状态向更多（晚期）效应表型转变，在持续 CMV 感染的情况下，这种转变更为明显。此外，我们发现衰老和 CMV 对耗尽的 TCRγδ+T 细胞的绝对计数都有影响。总的来说，我们的数据显示衰老和 CMV 持续存在对 DN 和 CD8+TCRγδ+T 细胞有明显影响，与 CD8+TCRαβ+T 细胞报告的情况类似，表明它们经历了类似的衰老过程。
