title: Chronic alcohol increases CD8+ T-cell immunosenescence in simian immunodeficiency virus-infected rhesus macaques.
abstract: 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.
authors.affiliation: Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
authors.forename: Paige S
authors.initials: PS
authors.lastname: Katz
authors.affiliation: Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA; Comprehensive Alcohol Research Center, Alcohol and Drug Abuse Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Siggins
authors.affiliation: Comprehensive Alcohol Research Center, Alcohol and Drug Abuse Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA; Department of Medicine, Section of Pulmonary/Critical Care & Allergy/Immunology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
authors.forename: Connie
authors.initials: C
authors.lastname: Porretta
authors.affiliation: Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
authors.forename: Megan L
authors.initials: ML
authors.lastname: Armstrong
authors.affiliation: Comprehensive Alcohol Research Center, Alcohol and Drug Abuse Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA; Department of Medicine, Section of Pulmonary/Critical Care & Allergy/Immunology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA; Department of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA; Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
authors.forename: Arnold H
authors.initials: AH
authors.lastname: Zea
authors.affiliation: School of Public Health, Biostatistics Program, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
authors.forename: Donald E
authors.initials: DE
authors.lastname: Mercante
authors.affiliation: Department of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA; Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA; New Orleans Louisiana Cancer Research Center, New Orleans, LA 70112, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Parsons
authors.affiliation: Comprehensive Alcohol Research Center, Alcohol and Drug Abuse Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA; Tulane National Primate Research Center, Tulane University, Covington, LA 70433, USA.
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Veazey
authors.affiliation: Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA; Comprehensive Alcohol Research Center, Alcohol and Drug Abuse Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Bagby
authors.affiliation: Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA; Comprehensive Alcohol Research Center, Alcohol and Drug Abuse Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA; Department of Medicine, Section of Pulmonary/Critical Care & Allergy/Immunology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
authors.forename: Steve
authors.initials: S
authors.lastname: Nelson
authors.affiliation: Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA; Comprehensive Alcohol Research Center, Alcohol and Drug Abuse Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Molina
authors.affiliation: Comprehensive Alcohol Research Center, Alcohol and Drug Abuse Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA; Department of Medicine, Section of Pulmonary/Critical Care & Allergy/Immunology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA; Department of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. Electronic address: dwelsh@lsuhsc.edu.
authors.forename: David A
authors.initials: DA
authors.lastname: Welsh
mesh_terms: D000437:Alcoholism / Q000276:immunology*; D000818:Animals; D063425:Binge Drinking / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D015658:HIV Infections / Q000276:immunology; D000068884:Immunosenescence / Q000187:drug effects* / Q000276:immunology; D007422:Intestines / Q000166:cytology / Q000276:immunology; D007963:Leukocytes, Mononuclear; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008253:Macaca mulatta; D008297:Male; D012367:RNA, Viral / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics; D016615:Telomere / Q000378:metabolism; D019562:Viral Load
chemical_list: D002492:Central Nervous System Depressants; D012367:RNA, Viral; D000431:Ethanol
keywords: Alcohol; Anti-retroviral therapy; Immune activation; Immunosenescence; SIV