title: Alterations in Activation, Cytotoxic Capacity and Trafficking Profile of Peripheral CD8 T Cells in Young Adult Binge Drinkers.
abstract: BACKGROUND
  Excess of alcohol consumption is a public health problem and has documented effects on the immune system of humans and animals. Animal and in vitro studies suggest that alcohol abuse changes CD8 T cell (CD8) characteristics, however it remains unknown if the CD8 profile of binge drinkers is different in terms of activation, trafficking and cytotoxic capacity.
  
  
  OBJECTIVE
  To analyze the peripheral CD8 cytotoxic capacity, activation and trafficking phenotypic profile of Mexican young adults with regard to alcohol consumption pattern.
  
  
  METHODS
  55 Mexican young adults were stratified as Light (20), Intermediate (18) or Binge drinkers (17) according to their reported alcohol consumption pattern. Blood samples were obtained and hematic biometry and liver enzyme analysis were performed. Peripheral CD8 profile was established by expression of Granzyme B (GB), CD137, CD127, CD69, TLR4, PD1, CCR2, CCR4, CCR5 and CXCR4 by FACS. Data was analyzed by ANOVA, posthoc DMS and Tamhane, and principal component analysis (PCA) with varimax rotation, p<0.05.
  
  
  RESULTS
  The Binge drinking group showed increased γGT together with increased expression of CD69 and reduced expression of TLR4, PD1, CCR2 and CXCR4 in peripheral CD8 cells. Other parameters were also specific to Binge drinkers. PCA established 3 factors associated with alcohol consumption: "Early Activation" represented by CD69 and TLR4 expression in the CD8 population; "Effector Activation" by CD69 expression in CD8 CD127(+)CD137(+) and CD8 CD25(+) CD137(+); and Trafficking by CXCR4 expression on total CD8 and CD8 GB(+)CXCR4(+), and CCR2 expression on total CD8. Binge drinking pattern showed low expression of Early Activation and Trafficking factors while Light drinking pattern exhibited high expression of Effector Activation factor.
  
  
  CONCLUSIONS
  Alcohol consumption affects the immune phenotype of CD8 cells since binge drinking pattern was found to be associated with high CD69 and low TLR4, CXCR4 and CCR2 expression, which suggest recent activation, decreased sensitivity to LPS and lower migration capacity in response to chemokines SDF-1 and MCP-1. These results indicate that a binge-drinking pattern of alcohol consumption may induce an altered immune profile that could be related with liver damage and the increased susceptibility to infection reported to this behavior.
authors.affiliation: Laboratory of Liver, Pancreas and Motility, Department of Experimental Medicine, Faculty of Medicine, Universidad Nacional Autónoma de México, Mexico City, Mexico.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Zaldivar Fujigaki
authors.affiliation: Dirección de Investigación, Hospital General de México "Dr. Eduardo Liceaga", Mexico City, Mexico.
authors.forename: América Guadalupe
authors.initials: AG
authors.lastname: Arroyo Valerio
authors.affiliation: Dirección de Investigación, Hospital General de México "Dr. Eduardo Liceaga", Mexico City, Mexico.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: López Alvarenga
authors.affiliation: Laboratory of Liver, Pancreas and Motility, Department of Experimental Medicine, Faculty of Medicine, Universidad Nacional Autónoma de México, Mexico City, Mexico.
authors.forename: Esperanza Gabriela
authors.initials: EG
authors.lastname: Gutiérrez Reyes
authors.affiliation: Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Mexico City, Mexico.
authors.forename: David
authors.initials: D
authors.lastname: Kershenobich
authors.affiliation: Laboratory of Liver, Pancreas and Motility, Department of Experimental Medicine, Faculty of Medicine, Universidad Nacional Autónoma de México, Mexico City, Mexico; Dirección de Investigación, Hospital General de México "Dr. Eduardo Liceaga", Mexico City, Mexico.
authors.forename: Joselin
authors.initials: J
authors.lastname: Hernández Ruiz
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000453:epidemiology / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D063425:Binge Drinking / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D002465:Cell Movement; D003602:Cytotoxicity, Immunologic; D003710:Demography; D005163:Factor Analysis, Statistical; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D037181:Lectins, C-Type / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D025341:Principal Component Analysis; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D055815:Young Adult; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D037181:Lectins, C-Type; D051197:Toll-Like Receptor 4; D000099192:CD69 Antigens; C495345:TLR4 protein, human