Alterations in high-dimensional T-cell profile and gene signature of immune aging in HIV-infected older adults without viremia.
Alterations in high-dimensional T-cell profile and gene signature of immune aging in HIV-infected older adults without viremia.
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随着年龄的增长，免疫系统的组成部分发生了变化。联合抗逆转录病毒疗法（ART）的引入通过抑制病毒复制和增加CD 4 + T细胞计数，大大提高了人类免疫缺陷病毒（HIV）感染者的预期寿命。免疫衰老样变化，包括记忆CD 8 + T细胞的扩增与衰老特征，在年轻的HIV感染者中报告，他们在ART中没有临床可检测到的病毒血症。然而，HIV感染是否影响老年HIV感染者的免疫衰老状态尚不清楚。在这里，我们通过检查外周血单核细胞（PBMC）中的一组衰老相关基因以及使用高维CyTOF分析深入分析CD 4+和CD 8 + T细胞亚群，在老年HIV感染者、HIV未感染者和体弱者（所有年龄≥65岁的人群）中解决了这个问题。年龄较大的HIV感染者的衰老相关基因（如PBMC中的CX 3CR 1）表达增加，这些基因与IL-7受体低效应记忆（IL-7 R α低EM）CD 8 + T细胞相关，CD 8 + T细胞是一种已知随年龄增长而扩增的细胞群。表达衰老、细胞毒性和炎症分子（包括CD 57、穿孔素和CX 3CR 1）的IL-7 R α低EM CD 8 + T细胞亚群，以及表达CD 161和CXCR 3（与具有复制能力的HIV-1携带细胞相关的分子）的记忆CD 4 + T细胞在老年HIV感染者中增加。总体而言，在ART中未检测到病毒血症的老年HIV感染者的PBMC中与年龄相关的免疫改变水平增加，表明HIV感染对老年HIV感染者的衰老具有持续影响，尽管病毒血症在临床上得到控制。高维CyTOF分析显示，与对照组相比，高表达细胞毒性、衰老和炎性分子（如穿孔素、CD 57、T-bet和CX 3CR 1）的IL-7受体α低效应记忆（IL-7 R α低EM）CD 8 + T细胞亚群在抗逆转录病毒治疗的无病毒血症的HIV感染个体中依次扩增。这些发现支持了尽管病毒血症得到控制，但HIV感染者可能存在免疫衰老驱动因素。
Alterations in the components of the immune system occur with aging. The introduction of combination antiretroviral therapy (ART) has dramatically improved life expectancy in human immunodeficiency virus (HIV) infected individuals by suppressing viral replication and increasing CD4+ T‐cell counts. Immunosenescence‐like changes, including the expansion of memory CD8+ T cells with senescent features, are reported in young HIV‐infected individuals who do not have clinically detectable viremia on ART. However, it is less known whether HIV infection affects the immunosenescent status in older HIV‐infected individuals. Here, we addressed this question in older HIV‐infected, HIV‐uninfected, and frail individuals (all groups age ≥65 years) by examining a set of aging‐associated genes in peripheral blood mononuclear cells (PBMCs) as well as by analyzing subsets of CD4+ and CD8+ T cells in depth using high‐dimensional CyTOF analysis. Older HIV‐infected individuals had increased expression of aging‐associated genes such as CX3CR1 in PBMCs which are related to IL‐7 receptor low effector memory (IL‐7Rαlow EM) CD8+ T cells, a cell population known to expand with age. The subsets of IL‐7Rαlow EM CD8+ T cells expressing senescent, cytotoxic, and inflammatory molecules, including CD57, perforin, and CX3CR1, as well as memory CD4+ T cells expressing CD161 and CXCR3, molecules associated with replication‐competent HIV‐1 harboring cells, were increased in older HIV‐infected individuals. Overall, older HIV‐infected individuals without detectable viremia on ART had augmented levels of age‐associated immune alterations in PBMCs, suggesting that HIV infection has a persistent impact on senescence in older HIV‐infected individuals despite the clinically controlled viremia. High‐dimensional CyTOF analysis reveals that subsets of IL‐7 receptor alpha low effector memory (IL‐7Rαlow EM) CD8+ T cells highly expressing cytotoxic, senescent, and inflammatory molecules like perforin, CD57, T‐bet and CX3CR1 expand in order HIV‐infected individuals without viremia on anti‐retroviral therapy compared to control groups. Those findings support the persistence of possible immune senescence driving factor(s) in order HIV‐infected individuals despite the control of viremia.
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影响因子：
13.1
作者：
McElhaney, Janet E.
通讯作者：
McElhaney, Janet E.
DOI：
10.1111/j.1532-5415.2008.01673.x
发表时间：
2008-05-01
影响因子：
6.3
作者：
De Fanis, Umberto;Wang, George C.;Leng, Sean X.
通讯作者：
Leng, Sean X.
影响因子：
4.6
作者：
Colle, JH;Moreau, JL;Thèze, J
通讯作者：
Thèze, J
影响因子：
7.3
作者：
Banga, Riddhima;Procopio, Francesco A.;Perreau, Matthieu
通讯作者：
Perreau, Matthieu
影响因子：
20.3
作者：
Deeks, SG;Kitchen, CMR;Hecht, FM
通讯作者：
Hecht, FM