Alterations in Activation, Cytotoxic Capacity and Trafficking Profile of Peripheral CD8 T Cells in Young Adult Binge Drinkers

Abstract

BackgroundExcess 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.AimTo analyze the peripheral CD8 cytotoxic capacity, activation and trafficking phenotypic profile of Mexican young adults with regard to alcohol consumption pattern.Methods55 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.ResultsThe 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.ConclusionsAlcohol 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.

Trends in Adult Alcohol Use and Binge Drinking in the Early 21st‐Century United States: A Meta‐Analysis of 6 National Survey Series

“…These discrepant survey results raise the question as to whether the trends in deaths from alcoholic liver disease and emergency department admissions are due to across-the-board increases in alcohol use and misuse, or whether changes in other risk factors, possibly coupled with demographic-specific increases in binge drinking, might explain these trends. For example, the prevalence of alcoholic liver disease could be impacted by population-level changes in obesity, viral hepatitis, demographic shifts that could include changes in the prevalence of genetic risk factors, shifts in beverage type and consumption patterns, or any combination of these factors (Ikeda et al, 1993, Wetterling et al, 1999, Hatton et al, 2009, Askgaard et al, 2015, Zaldivar Fujigaki et al, 2015). Similarly, the fact that the increases in emergency department admissions noted by White and colleagues (White et al, 2018) was largely concentrated among middle-aged people suggests that the increase might be driven by a combination of alcohol use and risk factors associated with age rather than acute alcohol consumption per se.…”

Correlation between alcohol use disorders, blood alcohol content, and length of stay in trauma patients

“…Further research has found that alcohol causes impairments in the human host immune system and delays the healing process. [ 16 17 18 19 20 21 ] However, we found no significant difference in LOS between trauma patients who were at risk for alcohol dependence and those who reported alcohol abstinence. HLOS could be affected by multiple factors including severity of disease, frequency of procedures, insurance type, bed status, and delayed discharge process and transfer.…”

Ethanol Exposure Up-Regulates PD-L1/PD-1 Immune Checkpoint Pathway and Promotes Mammary Tumor Development

“…perforin or granzymes). It has been shown that alcohol abuse may adversely affect T cell function ( 27 ), chronic alcohol exposure promotes systemic pro-inflammatory IFN-γ and IL-17 responses in mice ( 28 ), and alcohol consumption affect the immune phenotype of CD8 T cells ( 29 ) as well as the response of CD8 T cells against virus infection ( 30 ). In the current study our data confirmed the immunotoxic effects of ethanol on T cell function by showing that long-term ethanol exposure inhibited the cytotoxic effector function of CD8 T cells (with reduced CD8 T cells that produce IFN-γ, perforin or granzyme B molecules, Figure 4 ).…”