PDF(Pubmed)
Abstract：
Human cytomegalovirus (hCMV) is a ubiquitous latent persistent herpesvirus infecting 60-90% of the population worldwide. hCMV carriage in immunocompetent people is asymptomatic; thus, hCMV can be considered a component of normative aging. However, hCMV powerfully modulates many features of the immune, and likely other, systems and organs. Questions remain as to how hCMV carriage affects the human host. We used anti-CMV antibody titers as a stratifying criterion to examine the impact of \"intensity\" of hCMV infection as a potential biomarker of aging, inflammation, and immune homeostasis in a cohort of 247 participants stratified into younger (21-40 years) and older (> 65 years of age) groups. We showed that anti-CMV antibody titers increased with age and directly correlated to increased levels of soluble tumor necrosis factor (sTNFR) I in younger but not older participants. CD8 + cell numbers were reduced in the older group due to the loss in CD8 + T naïve (Tn) cells. In CMV carriers and, in particular, in anti-CMV Ab-high participants, this loss was mitigated or reversed by an increase in the numbers of CD8 + T effector memory (Tem) and T effector memory reexpressing CD45RA (Temra) cells. Analysis of CD38, HLA-DR, and CD57 expression revealed subset (CD4 or CD8)-specific changes that correlated with anti-CMV Ab levels. In addition, anti-CMV Ab levels predicted anti-CMV CD8 T cell responsiveness to different CMV open reading frames (ORFs) selectively in older participants, which correlated to the transcriptional order of expression of specific CMV ORFs. Implications of these results for the potential predictive value of anti-CMV Ab titers during aging are discussed.
摘要：
人巨细胞病毒（hCMV）是一种普遍存在的潜伏持久性疱疹病毒，感染了全球60-90％的人口。免疫能力强的人携带hCMV是无症状的；因此，hCMV可以被认为是规范老化的一个组成部分。然而,hCMV有力地调节免疫的许多特征，可能还有其他，系统和器官。关于hCMV携带如何影响人类宿主的问题仍然存在。我们使用抗CMV抗体滴度作为分层标准来检查hCMV感染的“强度”作为衰老的潜在生物标志物的影响，炎症,和免疫稳态在一个由247名参与者组成的队列中，分为年轻（21-40岁）和老年（>65岁）组。我们表明，抗CMV抗体滴度随年龄增长而增加，并与年轻但年龄较大的参与者中可溶性肿瘤坏死因子（sTNFR）I水平的增加直接相关。由于CD8+T初始(Tn)细胞的损失,在老年组中CD8+细胞数量减少。在CMV载体和，特别是,在抗CMV抗体高的参与者中，CD8+T效应记忆(Tem)和T效应记忆重表达CD45RA(Temra)细胞数量的增加减轻或逆转了这种损失.CD38,HLA-DR,和CD57表达显示与抗CMVAb水平相关的亚群（CD4或CD8）特异性变化。此外,抗CMVAb水平预测老年参与者对不同CMV开放阅读框（ORF）的抗CMVCD8T细胞反应，与特定CMVORF表达的转录顺序相关。讨论了这些结果对衰老过程中抗CMVAb滴度的潜在预测价值的影响。
