Chronic alcohol increases CD8+ T-cell immunosenescence in simian immunodeficiency virus-infected rhesus macaques.
Activated CD8+ T-cells correlate with viral load and may foretell antiretroviral therapy (ART) failure. HIV infection has been suggested to accelerate immunosenescence through chronic persistent inflammation. Alcohol-use disorders (AUD) are prevalent in persons living with HIV/AIDS (PLWHA). We tested the hypothesis that hazardous alcohol consumption accelerates immune activation and immunosenescence. Immune activation and immunosenescence were examined in CD8+ T lymphocytes (CD3+CD4-CD8+) isolated from intestinal biopsies, axillary lymph nodes, and peripheral blood mononuclear cells (PBMCs) of chronic binge alcohol (CBA)-consuming simian immunodeficiency virus (SIV)-infected male rhesus macaques with and without antiretroviral therapy (ART; CBA/ART+, CBA/ART-) and in PBMCs isolated from a cohort of PLWHA. Polychromatic flow cytometry was used to phenotype cells isolated from intestinal biopsies, lymph nodes, and peripheral blood from rhesus macaques and PLWHA. The Alcohol Use Disorders Identification Test (AUDIT) identified hazardous alcohol drinking in PLWHA. Viral load was determined by RT-qPCR and telomere length was measured using qPCR. PBMC CD8+ T-cell activation (CD38+HLA-DR+) and immunosenescence (CD28-) were increased over baseline levels (857% ± 334, p < 0.05; 398% ± 80, p < 0.05, respectively) only in CBA animals not receiving ART. Viral load correlated with CD8+ T-cell immunosenescence in macaque PBMCs (r(s) = 0.49, p = 0.02). Activated immunosenescent T-cell (CD8+CD38+CD28-) frequencies in PBMCs from PLWHA significantly correlated with AUDIT scores (r(s) = 0.75, p = 0.001), while no correlation was observed with CD4+ T-cell and AUDIT scores (r(s) = -0.24, p = 0.38). Activated immunosenescent T-cells had shorter telomeres than CD8+ T-cells (CD8+CD28+) from PLWHA. Our results suggest that CBA and AUD augment immune activation and immunosenescence in SIV-infected macaques and PLWHA.
['Katz|Paige S|PS|', 'Siggins|Robert W|RW|', 'Porretta|Connie|C|', 'Armstrong|Megan L|ML|', 'Zea|Arnold H|AH|', 'Mercante|Donald E|DE|', 'Parsons|Christopher|C|', 'Veazey|Ronald S|RS|', 'Bagby|Gregory J|GJ|', 'Nelson|Steve|S|', 'Molina|Patricia E|PE|', 'Welsh|David A|DA|']
D000437:Alcoholism D000818:Animals D063425:Binge Drinking D018414:CD8-Positive T-Lymphocytes D002492:Central Nervous System Depressants D000431:Ethanol D015658:HIV Infections D000068884:Immunosenescence D007422:Intestines D007963:Leukocytes, Mononuclear D008198:Lymph Nodes D008253:Macaca mulatta D008297:Male D012367:RNA, Viral D020133:Reverse Transcriptase Polymerase Chain Reaction D016097:Simian Acquired Immunodeficiency Syndrome D015302:Simian Immunodeficiency Virus D016615:Telomere D019562:Viral Load
Alcohol Immunosenescence Immune activation Anti-retroviral therapy SIV