American Thoracic Society, American Journal of Respiratory and Critical Care Medicine, 7(190), p. 744-755, 2014
DOI: 10.1164/rccm.201407-1226oc
Full text: Unavailable
Rationale: As overall survival improves, individuals with HIV infection become susceptible to other chronic diseases, including accelerated COPD. Objective: To determine whether individuals with HIV-associated COPD exhibit dysregulated lung mucosal T-cell immunity compared to controls. Methods: Using flow cytometry, we evaluated peripheral blood and lung mucosal T-cell immunity in 14 HIV+COPD+, 13 HIV+COPD- and 7 HIV-COPD+ individuals. Measurements and Main Results: HIV+COPD+ individuals demonstrated profound CD4+ T-cell depletion with reduced CD4:CD8 T-cell ratios in BAL-derived lung mononuclear cells (LMNC), not observed in PBMC, and diminished CD4+ T-cells absolute numbers, compared to controls. Further, HIV+COPD+ individuals demonstrated both decreased pulmonary HIV-specific and Staphylococcal Enterotoxin B (SEB)-reactive CD4+ memory responses, including loss of multi-functionality, compared to HIV+COPD- controls. In contrast, lung mucosal HIV-specific CD8+ T-cell responses were preserved. Lung CD4+ T-cells from HIV+COPD+ individuals expressed increased surface Fas death receptor (CD95) and programmed death-1 (PD-1), but similar BAL viral loads as controls. However, PD-1 expression inversely correlated with HIV-specific lung CD4+IFN-γ+ T-cell responses, suggesting functional exhaustion. Moreover, lung CD4+ T-cells from HIV+COPD+ patients demonstrated increased basal and HIV antigen-induced expression of the early apoptosis marker annexin V, compared to controls, which was significantly attenuated with anti-Fas blockade. Lastly, lung mucosal, but not blood, CD4+:CD8+ ratios from HIV+ patients significantly correlated with the FEV1, but not in HIV-COPD+ patients.