Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Massachusetts General Hospital and Harvard Medical School, Harvard University, Boston, Massachusetts.
Institute of Immunology, Friedrich-Loeffler-Institute, the Federal Research Institute for Animal Health, Greifswald, Isle of Riems, Germany.
Am J Respir Cell Mol Biol. 2021 Nov;65(5):513-520. doi: 10.1165/rcmb.2021-0168OC.
Smoking and human immunodeficiency virus 1 (HIV-1) infection are risk factors for chronic obstructive pulmonary disease (COPD), which is among the most common comorbid conditions in people living with HIV-1. HIV-1 infection leads to persistent expansion of CD8 T cells, and CD8 T cell-mediated inflammation has been implicated in COPD pathogenesis. In this study, we investigated the effects of HIV-1 infection and smoking on T-cell dynamics in patients at risk of COPD. BAL fluid, endobronchial brushings, and blood from HIV-1 infected and uninfected nonsmokers and smokers were analyzed by flow cytometry, and lungs were imaged by computed tomography. Chemokines were measured in BAL fluid, and CD8 T-cell chemotaxis in the presence of cigarette smoke extract was assessed . HIV-1 infection increased CD8 T cells in the BAL fluid, but this increase was abrogated by smoking. Smokers had reduced BAL fluid concentrations of the T cell-recruiting chemokines CXCL10 and CCL5, and cigarette smoke extract inhibited CXCL10 and CCL5 production by macrophages and CD8 T-cell transmigration . In contrast to the T cells in BAL fluid, CD8 T cells in endobronchial brushings were increased in HIV-1-infected smokers, which was driven by an accumulation of effector memory T cells in the airway mucosa and an increase in tissue-resident memory T cells. Mucosal CD8 T-cell numbers inversely correlated with lung aeration, suggesting an association with inflammation and remodeling. HIV-1 infection and smoking lead to retention of CD8 T cells within the airway mucosa.
吸烟和人类免疫缺陷病毒 1 型（HIV-1）感染是慢性阻塞性肺疾病（COPD）的危险因素，COPD 是 HIV-1 感染者最常见的合并症之一。HIV-1 感染导致 CD8 T 细胞持续扩增，而 CD8 T 细胞介导的炎症被认为与 COPD 的发病机制有关。在这项研究中，我们研究了 HIV-1 感染和吸烟对 COPD 高危人群 T 细胞动力学的影响。通过流式细胞术分析 HIV-1 感染和未感染的非吸烟者和吸烟者的支气管肺泡灌洗液、支气管内刷检和血液，并通过计算机断层扫描对肺部进行成像。测量支气管肺泡灌洗液中的趋化因子，并评估在香烟烟雾提取物存在的情况下 CD8 T 细胞的趋化性。HIV-1 感染增加了支气管肺泡灌洗液中的 CD8 T 细胞，但这种增加被吸烟所阻断。吸烟者支气管肺泡灌洗液中招募 T 细胞的趋化因子 CXCL10 和 CCL5 浓度降低，香烟烟雾提取物抑制巨噬细胞和 CD8 T 细胞迁移产生 CXCL10 和 CCL5。与支气管肺泡灌洗液中的 T 细胞相反，HIV-1 感染的吸烟者支气管内刷检中的 CD8 T 细胞增加，这是由气道黏膜中效应记忆 T 细胞的积累和组织驻留记忆 T 细胞的增加驱动的。黏膜 CD8 T 细胞数量与肺通气呈反比，提示与炎症和重塑有关。HIV-1 感染和吸烟导致 CD8 T 细胞在气道黏膜内滞留。
