Peculiar Phenotypic and Cytotoxic Features of Pulmonary Mucosal CD8 T Cells in People Living with HIV Receiving Long-Term Antiretroviral Therapy

Abstract People living with HIV have high burdens of chronic lung disease, cancers, and pulmonary infections despite antiretroviral therapy (ART). The rates tobacco smoking by people vastly exceed that the general population. Furthermore, we showed can persist within mucosa long-term ART. As CD8 T cell cytotoxicity is pivotal for controlling viral eliminating defective cells, explored phenotypic functional features versus peripheral blood cells in ART-treated HIV+ uninfected controls. Bronchoalveolar lavage fluid matched were obtained from asymptomatic smokers (n = 11) nonsmokers 15) 7) 10). subsets phenotypes assessed flow cytometry. Perforin/granzyme B content, degranulation (CD107a expression), against autologous Gag peptide-pulsed CD4 (Annexin V+) following vitro stimulation assessed. In all groups, enriched effector memory compared displayed higher levels activation (HLA-DR+) exhaustion (PD1+) markers. Significant reductions proportions senescent CD28−CD57+ observed only smokers. Pulmonary lower perforin expression ex vivo reduced granzyme nonsmokers. significantly less killing capacity than cells. Therefore, mucosal are more differentiated, activated, exhausted, potentially contributing to a suboptimal anti-HIV immune response lungs.