GC01-Immunology and Allergy Group, Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), 14004 Cordoba, Spain.
Department of Internal Medicine II, Centre for Medical Research, University of Tübingen, 72072 Tübingen, Germany.
Int J Mol Sci. 2021 Sep 15;22(18):9973. doi: 10.3390/ijms22189973.
Cytomegalovirus (CMV) latent infection and aging contribute to alterations in the function and phenotype of the T-cell pool. We have demonstrated that CMV-seropositivity is associated with the expansion of polyfunctional CD57+ T-cells in young and middle-aged individuals in response to different stimuli. Here, we expand our results on the effects of age and CMV infection on T-cell functionality in a cohort of healthy middle-aged and older individuals stratified by CMV serostatus. Specifically, we studied the polyfunctional responses (degranulation, IFN-γ and TNF-α production) of CD4+, CD8+, CD8+CD56+ (NKT-like), and CD4-CD8- (DN) T-cells according to CD57 expression in response to Staphylococcal Enterotoxin B (SEB). Our results show that CD57 expression by T-cells is not only a hallmark of CMV infection in young individuals but also at older ages. CD57+ T-cells are more polyfunctional than CD57- T-cells regardless of age. CMV-seronegative individuals have no or a very low percentages of cytotoxic CD4+ T-cells (CD1017a+) and CD4+CD57+ T-cells, supporting the notion that the expansion of these T-cells only occurs in the context of CMV infection. There was a functional shift in T-cells associated with CMV seropositivity, except in the NKT-like subset. Here, we show that the effect of CMV infection and age differ among T-cell subsets and that CMV is the major driving force for the expansion of highly polyfunctional CD57+ T-cells, emphasizing the necessity of considering CMV serology in any study of immunosenescence.
巨细胞病毒（CMV）潜伏感染和衰老导致 T 细胞库的功能和表型发生改变。我们已经证明，CMV 血清阳性与年轻和中年个体对不同刺激物的多效性 CD57+T 细胞的扩增有关。在这里，我们扩展了我们的研究结果，即年龄和 CMV 感染对 CMV 血清状态分层的健康中年和老年个体 T 细胞功能的影响。具体来说，我们研究了 CD4+、CD8+、CD8+CD56+（NKT 样）和 CD4-CD8-（DN）T 细胞根据 CD57 表达对葡萄球菌肠毒素 B（SEB）的多效性反应（脱颗粒、IFN-γ和 TNF-α产生）。我们的结果表明，T 细胞上的 CD57 表达不仅是年轻人 CMV 感染的标志，而且在老年时也是如此。无论年龄大小，CD57+T 细胞比 CD57-T 细胞具有更多的多效性。CMV 血清阴性个体没有或只有很少的细胞毒性 CD4+T 细胞（CD1017a+）和 CD4+CD57+T 细胞，这支持了只有在 CMV 感染的情况下才会扩增这些 T 细胞的观点。除了 NKT 样亚群外，与 CMV 血清阳性相关的 T 细胞存在功能转变。在这里，我们表明，CMV 感染和年龄对 T 细胞亚群的影响不同，并且 CMV 是高度多效性 CD57+T 细胞扩增的主要驱动力，强调在任何免疫衰老研究中都需要考虑 CMV 血清学。
