Leng Sean X, Qu Tao, Semba Richard D, Li Huifen, Yao Xu, Nilles Tricia, Yang Xi, Manwani Bhavish, Walston Jeremy D, Ferrucci Luigi, Fried Linda P, Margolick Joseph B, Bream Jay H
Division of Geriatric Medicine and Gerontology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
Age (Dordr). 2011 Dec;33(4):607-14. doi: 10.1007/s11357-011-9205-9. Epub 2011 Jan 28.
In immunocompetent individuals, cytomegalovirus (CMV) is thought to persist in a latent state in monocytes and myeloid progenitor cells, establishing a lifelong infection. In CMV-seropositive older adults, aging has been associated with both expansion of CMV pp65(495-503)-specific CD8(+) T cell clones and shrinkage of the T cell repertoire that characterize T cell immunosenescence. In fact it has been suggested that chronic CMV infection is a driving force in age-related T cell immunosenescence. In older adults, chronic CMV infection is conventionally diagnosed by positive IgG serology which does not distinguish between past and persistent infections. To better define the relationship between chronic CMV infection and expansion of CMV pp65(495-503)-specific CD8(+) T cells, we directly assessed CMV viral DNA in monocyte-enriched peripheral blood mononuclear cells in 16 HLA-A2-positive elderly volunteers (mean age = 83 years). While all participants had positive CMV IgG serology by enzyme-linked immunosorbent assays, only nine (56%) had detectable CMV DNA by nested polymerase chain reaction. These nine individuals had significantly higher percentages of CMV pp65(495-503) tetramer-positive CD8(+) T cells (median = 1.3%) than those without detectable CMV DNA (median = 0.1%; p < 0.001). Absolute CMV IgG antibody titers did not differ between these two groups (median = 54.6 vs 44.2 EU/ml, respectively, p = 0.4). CMV IgM titers were negative for all 16 participants, suggesting that recent primary CMV infection was unlikely. These results demonstrate a strong association between the presence of CMV DNA in peripheral monocytes and the expansion of CD8(+) T cells specific for the CMV immunodominant epitope pp65(495-503). Although the sample size in this study is relatively small, these findings provide initial evidence suggesting the heterogeneity of CMV IgG-seropositive older adult population and CMV viral DNA detection in peripheral monocytes as an informative tool to better understand the relationship between chronic CMV infection and T cell immunosenescence.
在免疫功能正常的个体中，巨细胞病毒（CMV）被认为在单核细胞和髓系祖细胞中以潜伏状态持续存在，从而建立终身感染。在CMV血清学阳性的老年人中，衰老与CMV pp65(495 - 503)特异性CD8(+) T细胞克隆的扩增以及表征T细胞免疫衰老的T细胞库缩小有关。事实上，有人提出慢性CMV感染是与年龄相关的T细胞免疫衰老的驱动力。在老年人中，慢性CMV感染通常通过IgG血清学阳性来诊断，这无法区分既往感染和持续感染。为了更好地界定慢性CMV感染与CMV pp65(495 - 503)特异性CD8(+) T细胞扩增之间的关系，我们直接评估了16名HLA - A2阳性老年志愿者（平均年龄 = 83岁）富含单核细胞的外周血单个核细胞中的CMV病毒DNA。虽然所有参与者通过酶联免疫吸附测定法检测CMV IgG血清学均为阳性，但通过巢式聚合酶链反应，只有9名（56%）检测到CMV DNA。这9名个体的CMV pp65(495 - 503)四聚体阳性CD8(+) T细胞百分比（中位数 = 1.3%）显著高于未检测到CMV DNA的个体（中位数 = 0.1%；p < 0.001）。这两组之间的CMV IgG抗体绝对滴度没有差异（中位数分别为54.6和44.2 EU/ml，p = 0.4）。所有16名参与者的CMV IgM滴度均为阴性，表明近期原发性CMV感染不太可能。这些结果表明外周单核细胞中CMV DNA的存在与针对CMV免疫显性表位pp65(495 - 503)的CD8(+) T细胞扩增之间存在强烈关联。尽管本研究中的样本量相对较小，但这些发现提供了初步证据，表明CMV IgG血清学阳性老年人群的异质性以及外周单核细胞中CMV病毒DNA检测作为一种信息工具，有助于更好地理解慢性CMV感染与T细胞免疫衰老之间的关系。
