Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryl.
Division of Geriatric Medicine and Gerontology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryl.
J Infect Dis. 2018 Jun 20;218(2):249-258. doi: 10.1093/infdis/jiy005.
Both aging and treated human immunodeficiency virus (HIV)-infected populations exhibit low-level chronic immune activation of unknown etiology, which correlates with morbidity and mortality. Cytomegalovirus (CMV) infection is common in both populations, but its relation to immune activation is unknown.
T cells from men who have sex with men (22 virologically suppressed HIV+, 20 HIV-) were stimulated with peptides spanning 19 CMV open reading frames, and intracellular cytokine responses were assessed. Soluble and cellular inflammatory markers were assessed by multiplex electrochemiluminescence and flow cytometry, respectively. Frailty was assessed by the Fried criteria.
All men had responses to CMV. Proportions of CMV-responsive T cells correlated strongly (r ≥ 0.6 or ≤ -0.6; P < .05) with immunologic markers, depending on donor HIV and frailty status. Markers significantly correlated in some groups after adjustment for multiple comparisons included interferon-γ, tumor necrosis factor-α, interleukin-6, and several chemokines in serum, and the proportion of activated T cells. The magnitude of the CD4 IL-2 response significantly predicted onset of frailty in HIV- nonfrail men, but not in HIV+ nonfrail men.
T-cell responses to CMV may strongly influence chronic immune activation in HIV-uninfected and virologically suppressed HIV-infected men, and may predict frailty in HIV-uninfected men.
衰老和接受治疗的人类免疫缺陷病毒(HIV)感染人群均表现出病因不明的低水平慢性免疫激活,这种免疫激活与发病率和死亡率相关。巨细胞病毒(CMV)在这两个群体中都很常见,但它与免疫激活的关系尚不清楚。
对男男性行为者(22 名病毒学抑制的 HIV 阳性,20 名 HIV 阴性)的 T 细胞进行了跨越 19 个 CMV 开放阅读框的肽段刺激,评估了细胞内细胞因子反应。通过多重电化学发光和流式细胞术分别评估可溶性和细胞炎症标志物。用 Fried 标准评估虚弱。
所有男性均对 CMV 有反应。CMV 反应性 T 细胞的比例与免疫标志物密切相关(r ≥ 0.6 或 ≤ -0.6;P <.05),这取决于供体的 HIV 和虚弱状态。在调整了多次比较后,一些组中的标志物显著相关,包括干扰素-γ、肿瘤坏死因子-α、白细胞介素-6 和几种趋化因子在血清中的比例,以及激活的 T 细胞的比例。CD4 IL-2 反应的幅度显著预测了 HIV 非虚弱男性的虚弱发生,但对 HIV 阳性非虚弱男性没有预测作用。
CMV 特异性 T 细胞反应可能强烈影响 HIV 未感染和病毒学抑制的 HIV 感染男性的慢性免疫激活,并可能预测 HIV 未感染男性的虚弱。