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 in vitro. 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 vitro. 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 (HIV-1) 感染是慢性阻塞性肺病 (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，CD8 ⁺ T^细胞介导的炎症与 COPD 发病机制有关。在这项研究中，我们调查了 HIV-1 感染和吸烟对 COPD 风险患者 T 细胞动力学的影响。通过流式细胞术分析 BAL 液、支气管内刷子以及来自 HIV-1 感染和未感染的非吸烟者和吸烟者的血液，并通过计算机断层扫描对肺部进行成像。趋化因子在 BAL 液和 CD8 ⁺在体外评估存在香烟烟雾提取物的 T 细胞趋化性。HIV-1 感染增加了 BAL 液中的 CD8 ⁺ T 细胞，但这种增加被吸烟消除了。吸烟者降低了 BAL 液中招募 T 细胞的趋化因子 CXCL10 和 CCL5 的浓度，而香烟烟雾提取物在体外抑制巨噬细胞产生 CXCL10 和 CCL5 以及 CD8 ⁺ T 细胞迁移。与 BAL 液中的 T 细胞相比，感染 HIV-1 的吸烟者的支气管内刷中的 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的增加驱动的T细胞。粘膜 CD8 ⁺T 细胞数量与肺通气呈负相关，表明与炎症和重塑有关。HIV-1 感染和吸烟导致 CD8 ⁺ T 细胞滞留在气道粘膜内。