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HIV Suppression Restores Lung Mucosal CD4+ T-Cell Viral Immunity and Resolves CD8+ Alveolitis in Patients at Risk for HIV-associated COPD.

HIV Suppression Restores Lung Mucosal CD4+ T-Cell Viral Immunity and Resolves CD8+ Alveolitis in Patients at Risk for HIV-associated COPD.
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Popescu I, Drummond MB, Gama L, Lambert A, Hoji A, Coon T, Merlo CA, Wise RA, Keruly J, Clements JE, Kirk GD, McDyer JF,


Popescu I, Drummond MB, Gama L, Lambert A, Hoji A, Coon T, Merlo CA, Wise RA, Keruly J, Clements JE, Kirk GD, McDyer JF, (click to view)

Popescu I, Drummond MB, Gama L, Lambert A, Hoji A, Coon T, Merlo CA, Wise RA, Keruly J, Clements JE, Kirk GD, McDyer JF,

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The Journal of infectious diseases 2016 9 9() pii

Abstract
BACKGROUND
 Lung CD4(+) depletion/dysfunction, CD8(+) alveolitis, smoking, and poor HIV control are features of HIV-associated COPD, but these changes have not been evaluated in smokers at-risk for COPD. We evaluated the impact of viral suppression following initiation of antiretroviral therapy (ART) on HIV-specific immunity and lung CD4:CD8 balance.

METHODS
 Using flow cytometry, we assessed lung/blood T-cell immunity in 12 actively- smoking HIV+ patients pre- and post-ART following viral suppression.

RESULTS
 HIV suppression resulted in enhanced lung/systemic HIV-specific CD4(+) immunity without significant changes in CD8(+) responses. We observed an increase in lung CD4:CD8 ratios and CD4(+) frequencies, decreased CD8(+) numbers, and resolution of CD8(+) alveolitis post -: ART, in 9/12 individuals. Viral suppression reduced Fas-receptor and programmed death-1 expression in lung CD4(+) T-cells, correlating with enhanced effector function and reduced susceptibility to apoptosis. HIV suppression rescued peripheral, but not lung, CD4(+) HIV-specific proliferation resulting in augmented effector multifunction.

DISCUSSION
 Together, our results demonstrate that HIV suppression restores lung mucosal HIV-specific CD4(+) T-cell multifunctional immunity and CD4:CD8 balance, often resolving CD8(+) alveolitis in active smokers. Peripheral expansion and redistribution of CD4(+) T-cells, and increased resistance to apoptosis are two mechanisms contributing to immunologic improvement following viral suppression in patients at risk for HIV-associated COPD.

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