Chronic Viral Illness Service and Research Institute of the McGill University Health Centre.
Department of Biological Sciences and BioMed Research Centre, University of Quebec at Montreal (UQAM).
AIDS. 2018 Oct 23;32(16):2279-2289. doi: 10.1097/QAD.0000000000001962.
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 CD4CCR6, Th1Th17 (CD4CCR6CCR4CXCR3), CD4CCR6CXCR3CCR4, and CD4CD32a 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.
在抗逆转录病毒治疗（ART）前时代，肺被认为是 HIV 复制的主要解剖部位之一。然而，在接受抑制性 ART 的个体中，其对 HIV 持续存在的贡献仍研究不足。
我们评估了 HIV 感染者（HIV）在接受长期抑制性 ART 治疗与未感染者中 HIV 的持续存在情况，并对肺部黏膜 CD4 T 细胞进行了全面描述。
从 24 名接受长期抑制性 ART（中位数：9 年）的 HIV 感染成人和 8 名无呼吸系统症状的健康志愿者中获得支气管肺泡灌洗液（BAL）、支气管活检和匹配的外周血。通过超灵敏 PCR 定量检测 HIV-DNA 和细胞相关 HIV-RNA，并用多参数流式细胞术对肺黏膜 CD4 T 细胞亚群进行了描述。
与血液相比，总 BAL 细胞中的 HIV-DNA 水平高 13 倍。重要的是，FACS 分选的 BAL CD4 T 细胞中的 HIV-DNA 水平高于外周血 CD4 T 细胞。HIV 感染者的 BAL CD4 T 细胞主要表现为效应记忆表型，而与血液相比，幼稚和终末分化细胞则较少。此外，BAL CD4 T 细胞表达更高水平的免疫激活（HLA-DR/CD38）和衰老（CD57）标志物。重要的是，BAL 富含被认为是 HIV 持续存在的优先细胞储库的 T 细胞亚群，包括记忆 CD4CCR6、Th1Th17（CD4CCR6CCR4CXCR3）、CD4CCR6CXCR3CCR4 和 CD4CD32a T 细胞。
在无呼吸系统症状的个体中，长期 ART 期间，肺部黏膜代表一个重要的免疫效应部位，其中富含活化和优先的 CD4 T 细胞亚群，这些细胞亚群对 HIV 持续存在具有重要作用。我们的发现为在黏膜组织中设计新的 HIV 清除策略带来了新的挑战。
