title: Chronic Binge Alcohol Administration Increases Intestinal T-Cell Proliferation and Turnover in Rhesus Macaques.
abstract: BACKGROUND
  Alcohol use results in changes in intestinal epithelial cell turnover and microbial translocation, yet less is known about the consequences on intestinal lymphocytes in the gut. Here, we compared T-cell subsets in the intestine of macaques before and after 3 months of chronic alcohol administration to examine the effects of alcohol on intestinal T-cell subsets.
  
  
  METHODS
  Rhesus macaques received either alcohol or isocaloric sucrose as a control treatment daily over a 3-month period via indwelling gastric catheters. Intestinal lymphocyte subsets were identified in biopsy samples by flow cytometry. Twenty-four hours prior to sampling, animals were inoculated with bromo-deoxyuridine (BrdU) to assess lymphocyte proliferation. Immunohistochemistry was performed on tissue samples to quantitate CD3+ cells.
  
  
  RESULTS
  Animals receiving alcohol had increased rates of intestinal T-cell turnover of both CD4+ and CD8+ T cells as reflected by increased BrdU incorporation. However, absolute numbers of T cells were decreased in intestinal tissues as evidenced by immunohistochemistry for total CD3 expression per mm(2) intestinal lamina propria in tissue sections. Combining immunohistochemistry and flow cytometry data showed that the absolute numbers of CD8+ T cells were significantly decreased, whereas absolute numbers of total CD4+ T cells were minimally decreased.
  
  
  CONCLUSIONS
  Collectively, these data indicate that alcohol exposure to the small intestine results in marked loss of CD3+ T cells, accompanied by marked increases in CD4+ and CD8+ T-cell proliferation and turnover, which we speculate is an attempt to maintain stable numbers of T cells in tissues. This suggests that alcohol results in accelerated T-cell turnover in the gut, which may contribute to premature T-cell senescence. Further, these data indicate that chronic alcohol administration results in increased levels of HIV target cells (proliferating CD4+ T cells) that may support higher levels of HIV replication in intestinal tissues.
authors.affiliation: Tulane National Primate Research Center, Tulane University School of Medicine, Covington, Louisiana.
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Veazey
authors.affiliation: Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, Louisiana.|Comprehensive Alcohol Research Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana.
authors.forename: Angela
authors.initials: A
authors.lastname: Amedee
authors.affiliation: Tulane National Primate Research Center, Tulane University School of Medicine, Covington, Louisiana.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Tulane National Primate Research Center, Tulane University School of Medicine, Covington, Louisiana.
authors.forename: M
authors.initials: M
authors.lastname: Bernice Kaack
authors.affiliation: Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, Louisiana.|Comprehensive Alcohol Research Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana.
authors.forename: Constance
authors.initials: C
authors.lastname: Porretta
authors.affiliation: Tulane National Primate Research Center, Tulane University School of Medicine, Covington, Louisiana.
authors.forename: Jason
authors.initials: J
authors.lastname: Dufour
authors.affiliation: Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, Louisiana.|Comprehensive Alcohol Research Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana.
authors.forename: David
authors.initials: D
authors.lastname: Welsh
authors.affiliation: Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, Louisiana.|Comprehensive Alcohol Research Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana.
authors.forename: Kyle
authors.initials: K
authors.lastname: Happel
authors.affiliation: Tulane National Primate Research Center, Tulane University School of Medicine, Covington, Louisiana.
authors.forename: Bapi
authors.initials: B
authors.lastname: Pahar
authors.affiliation: Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, Louisiana.|Comprehensive Alcohol Research Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana.
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Molina
authors.affiliation: Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, Louisiana.|Comprehensive Alcohol Research Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana.
authors.forename: Steve
authors.initials: S
authors.lastname: Nelson
authors.affiliation: Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, Louisiana.|Comprehensive Alcohol Research Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Bagby
mesh_terms: D000818:Animals; D063425:Binge Drinking / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects* / Q000502:physiology; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D008253:Macaca mulatta; D008297:Male; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*
keywords: AIDS; Animal Models; Chronic Binge Drinking; Ethanol; Mucosal Immunology; Rhesus Macaque; T Cell