Background: HIV infection is associated with increased risk to lower respiratory tract infections (LRTI). However, the impact of HIV infection on immune cell populations in the lung is not well defined. We sought to comprehensively characterise the impact of HIV infection on immune cell populations in the lung. Methods: Twenty HIV-uninfected controls and 17 HIV-1 infected ART-naïve adults were recruited from Queen Elizabeth Central Hospital, Malawi. Immunophenotyping of lymphocyte and myeloid cell populations was done on bronchoalveolar lavage fluid and peripheral blood cells. Results: We found that the numbers of CD8 + T cells, B cells and gamma delta T cells were higher in BAL fluid of HIV-infected adults compared to HIV-uninfected controls (all p<0.05). In contrast, there was no difference in the numbers of alveolar CD4 + T cells in HIV-infected adults compared to HIV-uninfected controls (p=0.7065). Intermediate monocytes were the predominant monocyte subset in BAL fluid (HIV-, 63%; HIV+ 81%), while the numbers of classical monocytes was lower in HIV-infected individuals compared to HIV-uninfected adults (1 × 10 5 vs. 2.8 × 10 5 cells/100ml of BAL fluid, p=0.0001). The proportions of alveolar macrophages and myeloid dendritic cells was lower in HIV-infected adults compared to HIV-uninfected controls (all p<0.05). Conclusions: Chronic HIV infection is associated with broad alteration of immune cell populations in the lung, but does not lead to massive depletion of alveolar CD4 + T cells. Disruption of alveolar immune cell homeostasis likely explains in part the susceptibility for LRTIs in HIV-infected adults.

HIV-infected adults are at an increased risk to lower respiratory tract infections (LRTIs). CD8 + CD161 ++ TCRvα7.2 + T cells are an innate-like T cell subset that are thought to play an important role in early defense against pathogens in the respiratory tract. HIV infection leads to irreversible depletion of these cells in peripheral blood, however, its impact on this subset in the human airway is still unclear. Here, we show presence of CD103 expressing CD8 + CD161 ++ TCRvα7.2 + T cells in the airway that exhibited a distinct cytokine functional profile compared to their CD103 − airway counterparts and those from peripheral blood. These CD103 expressing airway CD8 + CD161 ++ TCRvα7.2 + T cells were selectively depleted in untreated HIV-infected adults compared to healthy controls. Their frequency was positively correlated with frequency of airway CD4 + T cells. Furthermore, the frequency of airway CD8 + CD161 ++ TCRvα7.2 + T cells was also inversely correlated with HIV plasma viral load, while suppressive antiretroviral therapy (ART) resulted in restoration of airway CD8 + CD161 ++ TCRvα7.2 + T cells. Our findings show that CD103 expressing airway CD8 + CD161 ++ TCRvα7.2 + T cells are functionally distinct and are preferentially depleted during untreated asymptomatic HIV infection. Depletion of CD103 expressing airway CD8 + CD161 ++ TCRvα7.2 + T cells, at a major portal of pathogen entry, could partly contribute to the increased propensity for opportunistic LRTIs observed in untreated HIV-infected adults.