Division of BioMedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, Canada.
Front Immunol. 2018 Feb 15;9:201. doi: 10.3389/fimmu.2018.00201. eCollection 2018.
Antiretroviral therapy (ART) effectively extends the life expectancy of human immunodeficiency virus (HIV)-infected individuals; however, age-related morbidities have emerged as major clinical concerns. In this context, coinfection with cytomegalovirus (CMV) accelerates immune senescence and elevates risk for other age-related morbidities, possibly through increased inflammation. We investigated potential relationships between CMV memory inflation, immune senescence, and inflammation by measuring markers of inflammation and telomere lengths of different lymphocyte subsets in HIV-infected individuals seropositive for anti-CMV antibodies. Our study cohort consists mainly of middle aged men who have sex with men (MSM) and heterosexuals who are stable under long-term ART. Median levels of IL-6, TNF-α, and CRP were significantly higher in those coinfected with CMV. Lymphocyte telomere length in general correlated with age, but for 32/32 subjects tested, there was a consistent hierarchy of telomere lengths with CD8 T cells' shorter than the general lymphocyte population, CD57CD8 T cells' shorter than CD8 T cells' and CMV-specific CD57CD8 T cells' the shortest of all. Telomeres of HIV-specific CD8 T cells were longer than those of CMV-specific CD8 T cells in all cases tested and over 10 years, CMV-specific CD8 T cell telomeres of two HIV-infected individuals eroded faster than those of HIV-specific CD8 T cells. These data indicate that CMV-specific CD8 T cells of HIV-infected individuals are the lymphocytes closest to telomere-imposed replicative senescence. Exhaustive proliferation of CMV-specific CD8 T cells in HIV-infected individuals is a potential source of senescent lymphocytes affecting systemic immune function and inflammation.
抗逆转录病毒疗法（ART）有效地延长了人类免疫缺陷病毒（HIV）感染者的预期寿命；然而，与年龄相关的疾病已成为主要的临床关注点。在这种情况下，巨细胞病毒（CMV）合并感染加速了免疫衰老，并增加了其他与年龄相关的疾病的风险，这可能是通过增加炎症实现的。我们通过测量 HIV 感染个体中抗 CMV 抗体阳性的不同淋巴细胞亚群的炎症标志物和端粒长度，研究了 CMV 记忆膨胀、免疫衰老和炎症之间的潜在关系。我们的研究队列主要由中年男男性行为者（MSM）和长期接受 ART 治疗稳定的异性恋者组成。CMV 合并感染患者的 IL-6、TNF-α 和 CRP 中位水平明显升高。淋巴细胞端粒长度通常与年龄相关，但在 32/32 名接受测试的受试者中，存在着 CD8 T 细胞短于普通淋巴细胞群、CD57CD8 T 细胞短于 CD8 T 细胞以及 CMV 特异性 CD57CD8 T 细胞最短的一致端粒长度等级。在所有测试的情况下，HIV 特异性 CD8 T 细胞的端粒都比 CMV 特异性 CD8 T 细胞的端粒长，并且在超过 10 年的时间里，两名 HIV 感染个体的 CMV 特异性 CD8 T 细胞端粒的侵蚀速度比 HIV 特异性 CD8 T 细胞的端粒快。这些数据表明，HIV 感染个体的 CMV 特异性 CD8 T 细胞是最接近端粒限制复制衰老的淋巴细胞。CMV 特异性 CD8 T 细胞在 HIV 感染个体中的过度增殖是影响全身免疫功能和炎症的衰老淋巴细胞的潜在来源。
