HIV persistence in mucosal CD4+ T cells within the lungs of adults receiving long-term suppressive antiretroviral therapy.
HIV persistence in mucosal CD4+ T cells within the lungs of adults receiving long-term suppressive antiretroviral therapy.
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DOI：
10.1097/qad.0000000000001962
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发表时间：
2018-10-23
期刊：
影响因子：
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通讯作者：
Jenabian MA
中科院分区：
文献类型：
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作者：
Costiniuk CT;Salahuddin S;Farnos O;Olivenstein R;Pagliuzza A;Orlova M;Schurr E;De Castro C;Bourbeau J;Routy JP;Ancuta P;Chomont N;Jenabian MA
在抗逆转录病毒治疗（ART）之前，肺在历史上被认为是HIV复制的主要解剖部位之一。然而，他们的贡献，艾滋病毒在抑制性抗逆转录病毒治疗的个人持续存在的研究仍然不足。我们评估了接受长期抑制性ART的HIV感染者（HIV+）与未感染者的HIV持续性和肺粘膜CD 4 + T细胞的综合特征。支气管肺泡灌洗（BAL），支气管活检，和匹配的外周血从n = 24接受长期抑制性ART（中位数：9年）和n = 8健康志愿者没有呼吸道症状的HIV感染的成年人。 采用超灵敏PCR定量检测HIV-DNA和细胞相关HIV-RNA，采用多参数流式细胞术检测肺粘膜CD 4 + T细胞亚群。与血液相比，总BAL细胞中的HIV-DNA水平高13倍。重要的是，来自BAL的FACS分选的CD 4 + T细胞与外周CD 4 + T细胞相比含有更高水平的HIV-DNA。HIV+个体中的BAL CD 4 + T细胞的特征主要是效应记忆表型，而与血液相比，幼稚和终末分化细胞的代表性不足。此外，BAL CD 4 + T细胞表达更高水平的免疫活化（HLA-DR/CD 38）和衰老（CD 57）标志物。重要的是，BAL中富含T细胞亚群，被认为是优先的细胞HIV储库，包括记忆性CD 4 + CCR 6+、Th 1 Th 17（CD 4 + CCR 6 + CCR 4 − CXCR 3+）、CD 4 + CCR 6 + CXCR 3 − CCR 4 −和CD 4 + CD 32a + T细胞。肺粘膜代表了一个重要的免疫效应部位，在没有呼吸道症状的个体中，在长期ART期间，高度富集活化和优先的CD 4 + T细胞亚群，用于HIV持续存在。我们的研究结果提出了新的挑战，在粘膜组织中的新的HIV根除策略的设计。
The lungs were historically identified as one of the major anatomic sites for HIV replication in the pre-antiretroviral therapy (ART) era. However, their contribution to HIV persistence in individuals under suppressive ART remains understudied. We assessed HIV persistence and comprehensively characterized pulmonary mucosal CD4+ T cells in HIV-infected (HIV+) individuals receiving long-term suppressive ART versus uninfected participants. Bronchoalveolar lavage (BAL), bronchial biopsies, and matched peripheral blood were obtained from n = 24 HIV-infected adults receiving long-term suppressive ART (median: 9 years) and n = 8 healthy volunteers without respiratory symptoms. HIV-DNA and cell-associated HIV-RNA were quantified by ultra-sensitive PCR, and lung mucosal CD4+ T-cell subsets were characterized by multiparameter flow cytometry. The levels of HIV-DNA were 13-fold higher in total BAL cells compared to blood. Importantly, FACS-sorted CD4+ T cells from BAL contained greater levels of HIV-DNA compared to peripheral CD4+ T cells. BAL CD4+ T cells in HIV+ individuals were characterized mostly by an effector memory phenotype, whereas naive and terminally differentiated cells were underrepresented compared to blood. Furthermore, BAL CD4+ T cells expressed higher levels of immune activation (HLA-DR/CD38) and senescence (CD57) markers. Importantly, BAL was enriched in T-cell subsets proposed to be preferential cellular HIV reservoirs, including memory CD4+CCR6+, Th1Th17 (CD4+CCR6+CCR4−CXCR3+), CD4+CCR6+CXCR3−CCR4−, and CD4+CD32a+ T cells. The pulmonary mucosa represents an important immunological effector site highly enriched in activated and preferential CD4+ T-cell subsets for HIV persistence during long-term ART in individuals without respiratory symptoms. Our findings raise new challenges for the design of novel HIV eradication strategies in mucosal tissues.