Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
Graduate Program in Immunology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
J Virol. 2024 Oct 22;98(10):e0116724. doi: 10.1128/jvi.01167-24. Epub 2024 Sep 4.
Cytomegalovirus (CMV)-seropositive adults have large T cell responses to a wide range of CMV proteins; these responses have been associated with chronic inflammation and frailty in people with or without HIV infection. We analyzed the relationships between chronic HIV infection, frailty, and the breadth and polyfunctionality of CD4 and CD8 T cell responses to CMV. Peripheral blood mononuclear cells from 42 men (20 without HIV and 22 with virologically suppressed HIV) in the Multicenter AIDS Cohort Study (MACS) were stimulated with peptide pools spanning 19 CMV open reading frames (ORFs). As measured by flow cytometry and intracellular cytokine staining for IFN-γ, TNF-α, and IL-2, CD8 T cells from men with HIV responded to significantly more CMV ORFs than those from men without HIV. This was primarily due to a broader response to ORFs that are expressed during the late phase of CMV replication. The number of ORFs to which a participant's T cells responded was positively correlated with the sum of all that individual's T cell responses; these correlations were weaker in men with than without HIV. Polyfunctional CMV-specific CD4 responses (production of more than one cytokine) were significantly lower in men with than without HIV. Frailty status did not substantially affect the breadth or magnitude of the CMV-specific T cell responses. These results suggest that immune control of CMV infection is affected more by chronic HIV infection than by frailty. The differences between men with and without HIV were similar to those reported between young and older adults without HIV.
T cell responses to chronic cytomegalovirus (CMV) infection have significant biological and clinical implications in HIV infection and aging. Here, we systematically analyzed the breadth, magnitude, and polyfunctionality of T cell responses to multiple CMV antigens in men with and without HIV in the Multicenter AIDS Cohort Study (MACS), a longstanding study of the natural and treated history of HIV-1 infection in men who have sex with men. We found that the breadth and polyfunctionality of T cell responses to CMV were different between men with chronic, treated HIV and those without HIV. The reason for these differences is unknown, but these findings suggest that people with treated HIV may have more frequent CMV reactivation than people without HIV. Differences between people with and without HIV also resembled differences reported between young and older adults without HIV, supporting a role for the immune responses to CMV in the aging process.
巨细胞病毒（CMV）-血清阳性的成年人对广泛的 CMV 蛋白具有大 T 细胞反应；这些反应与 HIV 感染或未感染者的慢性炎症和虚弱有关。我们分析了慢性 HIV 感染、虚弱与 CMV 对 CD4 和 CD8 T 细胞反应的广度和多功能性之间的关系。从多中心 AIDS 队列研究（MACS）中的 42 名男性（20 名无 HIV 和 22 名病毒学抑制的 HIV）的外周血单核细胞中，用跨越 19 个 CMV 开放阅读框（ORF）的肽池刺激。通过流式细胞术和细胞内细胞因子染色测量 IFN-γ、TNF-α 和 IL-2，HIV 男性的 CD8 T 细胞对 CMV ORF 的反应明显多于无 HIV 男性。这主要是由于对 CMV 复制后期表达的 ORF 反应更广泛。参与者的 T 细胞反应的 ORF 数量与个体 T 细胞反应的总和呈正相关；在有 HIV 的男性中，这些相关性比没有 HIV 的男性更弱。CMV 特异性 CD4 反应（产生一种以上细胞因子）在有 HIV 的男性中明显低于无 HIV 的男性。虚弱状态并未显著影响 CMV 特异性 T 细胞反应的广度或幅度。这些结果表明，CMV 感染的免疫控制受慢性 HIV 感染的影响大于虚弱的影响。有 HIV 和无 HIV 的男性之间的差异与无 HIV 的年轻和老年成年人之间报告的差异相似。
慢性巨细胞病毒（CMV）感染的 T 细胞反应在 HIV 感染和衰老中具有重要的生物学和临床意义。在这里，我们在多中心 AIDS 队列研究（MACS）中系统地分析了 HIV 感染和衰老的男性中慢性、治疗性 HIV 和无 HIV 的男性中 CMV 多种抗原的 T 细胞反应的广度、幅度和多功能性，这是一项对男男性行为者中 HIV-1 感染的自然和治疗史进行研究的长期研究。我们发现，慢性、治疗性 HIV 男性与无 HIV 男性的 CMV 反应的广度和多功能性不同。这些差异的原因尚不清楚，但这些发现表明，接受治疗的 HIV 患者可能比没有 HIV 的患者更频繁地发生 CMV 再激活。有 HIV 和无 HIV 的人之间的差异也类似于无 HIV 的年轻和老年成年人之间报告的差异，这表明 CMV 的免疫反应在衰老过程中起作用。
