Dynamics of pulmonary mucosal cytotoxic CD8 T-cells in people living with HIV under suppressive antiretroviral therapy

• Published in: Respiratory research 2024-06, Vol.25 (1), p.240-15
• Main Authors: Alexandrova, Yulia, Yero, Alexis, Olivenstein, Ronald, Orlova, Marianna, Schurr, Erwin, Estaquier, Jerome, Costiniuk, Cecilia T, Jenabian, Mohammad-Ali
• Format: Article
• Language: English
• Subjects: Adult; Anti-HIV Agents - therapeutic use; Anti-Retroviral Agents - therapeutic use; Antiviral agents; Bronchoalveolar Lavage Fluid - immunology; Care and treatment; CD8 T-cells; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Dosage and administration; Female; Health aspects; HIV; HIV Infections - drug therapy; HIV Infections - immunology; HIV patients; Humans; Infection control; Lung; Lung - drug effects; Lung - immunology; Lung - metabolism; Lung diseases; Male; Methods; Middle Aged; People living with HIV (PLWH); Prevention; Pulmonary immunity; Respiratory Mucosa - drug effects; Respiratory Mucosa - immunology; Respiratory Mucosa - metabolism; Risk factors; Smokers; Smoking; Smoking - adverse effects; T-Lymphocytes, Cytotoxic - drug effects; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Cytotoxic - metabolism
• ISSN: 1465-9921; 1465-993X; 1465-993X
• DOI: 10.1186/s12931-024-02859-2

Despite the success of antiretroviral therapy (ART), people living with HIV (PLWH) suffer from a high burden of pulmonary diseases, even after accounting for their smoking status. Cytotoxic CD8 T-cells are likely implicated in this phenomenon and may act as a double-edged sword. While being essential in viral infection control, their hyperactivation can also contribute to lung mucosal tissue damage. The effects of HIV and smoking on pulmonary mucosal CD8 T-cell dynamics has been a neglected area of research, which we address herein. Bronchoalveolar lavage (BAL) fluid were obtained from ART-treated PLWH (median duration of supressed viral load: 9 years; smokers: n = 14; non-smokers: n = 21) and HIV-uninfected controls (smokers: n = 11; non-smokers: n = 20) without any respiratory symptoms or active infection. Lymphocytes were isolated and CD8 T-cell subsets and homing markers were characterized by multiparametric flow cytometry. Both smoking and HIV infection were independently associated with a significant increase in frequencies of total pulmonary mucosal CD8 T-cell. BAL CD8 T-cells were primarily CD69 + expressing CD103 and/or CD49a, at least one of the two granzymes (GzmA/GzmB), and little Perforin. Higher expression levels of CD103, CD69, and GzmB were observed in smokers versus non-smokers. The ex vivo phenotype of GzmA + and GzmB + cells revealed increased expression of CD103 and CXCR6 in smokers, while PLWH displayed elevated levels of CX3CR1 compared to controls. Smoking and HIV could promote cytotoxic CD8 T-cell retention in small airways through different mechanisms. Smoking likely increases recruitment and retention of GzmB + CD8 Trm via CXCR6 and CD103. Heightened CX3CR1 expression could be associated with CD8 non-Trm recruitment from the periphery in PLWH.