Müller-Durovic Bojana, Grählert Jasmin, Devine Oliver P, Akbar Arne N, Hess Christoph
University Hospital Basel, Department of Biomedicine, Basel, Switzerland.
Division of Infection and Immunity, University College London, London, UK.
Aging (Albany NY). 2019 Jan 27;11(2):724-740. doi: 10.18632/aging.101774.
Natural killer cells lacking expression of CD56 (CD56 NK cells) have been described in chronic HIV and hepatitis C virus infection. Features and functions of CD56 NK cells in the context of latent infection with CMV and / or EBV with age are not known. In a cohort of healthy donors >60 years of age, we found that co-infection with CMV and EBV drives expansion of CD56 NK cells. Functionally, CD56 NK cells displayed reduced cytotoxic capacity and IFN-γ production, a feature that was enhanced with CMV / EBV co-infection. Further, the frequency of CD56 NK cells correlated with accumulation of end-stage-differentiated T cells and a reduced CD4 / CD8 T cell ratio, reflecting an immune risk profile. CD56 NK cells had a mature phenotype characterized by low CD57 and KIR expression and lacked characteristics of cell senescence. No changes in their activating NK cell receptor expression, and no upregulation of the negative co-stimulation receptors PD-1 or TIM-3 were observed. In all, our data identify expansion of dysfunctional CD56 NK cells in CMVEBV elderly individuals suggesting that these cells may function as shape-shifters of cellular immunity and argue for a previously unrecognized role of EBV in mediating immune risk in the elderly.
在慢性HIV和丙型肝炎病毒感染中已描述了缺乏CD56表达的自然杀伤细胞（CD56自然杀伤细胞）。在巨细胞病毒（CMV）和/或EB病毒潜伏感染背景下，CD56自然杀伤细胞随年龄变化的特征和功能尚不清楚。在一组年龄大于60岁的健康供体中，我们发现CMV和EB病毒的共同感染驱动了CD56自然杀伤细胞的扩增。在功能上，CD56自然杀伤细胞表现出细胞毒性能力和IFN-γ产生降低，这一特征在CMV/EB病毒共同感染时增强。此外，CD56自然杀伤细胞的频率与终末分化T细胞的积累以及CD4/CD8 T细胞比值降低相关，反映出一种免疫风险特征。CD56自然杀伤细胞具有以低CD57和杀伤细胞免疫球蛋白样受体（KIR）表达为特征的成熟表型，并且缺乏细胞衰老的特征。未观察到其活化性自然杀伤细胞受体表达的变化，也未观察到负性共刺激受体PD-1或T细胞免疫球蛋白黏蛋白域分子3（TIM-3）的上调。总之，我们的数据表明在CMV-EBV感染的老年人中功能失调的CD56自然杀伤细胞会扩增，提示这些细胞可能作为细胞免疫的变形者发挥作用，并支持EB病毒在介导老年人免疫风险中存在先前未被认识的作用。
