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American Thoracic Society, American Journal of Respiratory and Critical Care Medicine, 7(190), p. 744-755, 2014

DOI: 10.1164/rccm.201407-1226oc

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Activation-induced Cell Death Drives Profound Lung CD4+T-Cell Depletion in HIV-associated Chronic Obstructive Pulmonary Disease

This paper was not found in any repository, but could be made available legally by the author.
This paper was not found in any repository, but could be made available legally by the author.

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Data provided by SHERPA/RoMEO

Abstract

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.