Department of Medicine, University of California San Francisco, San Francisco, California, United States of America.
PLoS One. 2010 Jan 29;5(1):e8886. doi: 10.1371/journal.pone.0008886.
In healthy, HIV seronegative, CMV seropositive adults, a large proportion of T cells are CMV-specific. High-level CMV-specific T cell responses are associated with accelerated immunologic aging ("immunosenesence") in the elderly population. The impact of untreated and treated HIV infection on the frequency of these cells remains undefined.
METHODOLOGY/PRINCIPAL FINDINGS: We measured the proportion of CD4+ and CD8+ T cells responding to CMV pp65 and IE proteins was measured using flow cytometry in 685 unique HIV seronegative and seropositive individuals. The proportion of CMV-specific CD8+ T cells was consistently higher in the HIV-seropositive subjects compared to the HIV-seronegative subjects. This HIV effect was observed even in patients who lacked measurable immunodeficiency. Among the HIV-seropositive subjects, CMV-specific CD8+ T cell responses were proportionately lower during recent infection, higher during chronic untreated infection and higher still during long-term antiretroviral treated infection. The CD8+ T cell response to just two CMV proteins (pp65 and IE) was approximately 6% during long-term therapy, which was over twice that seen in HIV-seronegative persons. CMV-specific CD4+ T cell responses followed the same trends, but the magnitude of the effect was smaller.
CONCLUSIONS/SIGNIFICANCE: Long-term successfully treated HIV infected patients have remarkably high levels of CMV-specific effector cells. These levels are similar to that observed in the elderly, but occur at much younger ages. Future studies should focus on defining the potential role of the CMV-specific inflammatory response in non-AIDS morbidity and mortality, including immunosenescence.
在健康、HIV 血清阴性、CMV 血清阳性的成年人中，很大一部分 T 细胞是 CMV 特异性的。高水平的 CMV 特异性 T 细胞反应与老年人群的免疫衰老（“免疫衰老”）加速有关。未经治疗和治疗的 HIV 感染对这些细胞频率的影响仍未确定。
方法/主要发现：我们使用流式细胞术测量了 685 名独特的 HIV 血清阴性和阳性个体对 CMV pp65 和 IE 蛋白的 CD4+和 CD8+T 细胞反应的比例。与 HIV 血清阴性个体相比，HIV 血清阳性个体的 CMV 特异性 CD8+T 细胞比例始终更高。即使在没有可测量免疫缺陷的患者中，也观察到了这种 HIV 效应。在 HIV 血清阳性个体中，CMV 特异性 CD8+T 细胞反应在近期感染时比例较低，在慢性未经治疗的感染时较高，在长期抗逆转录病毒治疗的感染时仍然较高。长期治疗期间，对仅两种 CMV 蛋白（pp65 和 IE）的 CD8+T 细胞反应约为 6%，是 HIV 血清阴性个体的两倍多。CMV 特异性 CD4+T 细胞反应遵循相同的趋势，但影响的幅度较小。
结论/意义：长期成功治疗的 HIV 感染患者具有极高水平的 CMV 特异性效应细胞。这些水平与老年人观察到的水平相似，但发生在更年轻的年龄。未来的研究应集中于定义 CMV 特异性炎症反应在非艾滋病发病率和死亡率中的潜在作用，包括免疫衰老。
