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

Background 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.

Methods 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.

Results 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.

Conclusion 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.