Expansions of CD8+CD28-and CD8+TcRV beta 5.2+T cells in peripheral blood of heavy alcohol drinkers

Background: Despite heavy alcohol consumption, only a low percentage of hea vy drinkers develop liver disease. Imbalances in T-cell subsets and iron me tabolism parameters are common findings in heavy drinkers, yet the possible role played by discrete T-lymphocyte subsets under heavy alcohol consumpti on remains unclear. Methods: To gain new insights into the possible role played by T lymphocyte s during alcohol consumption, characterization of CD28 expression and TcR r epertoire in peripheral blood CD4+ and CD8+ T cells by two and three-color flow cytometry was performed. A group of heavy alcohol drinkers (AHD, n = 7 1) and a group of age-matched controls (n = 81), both HLA-phenotyped and HF E-genotyped, constituted the groups under study. Results: Marked expansions of CD28- T cells within the CD8+ but not the CD4 + T-cell pool were observed in AHD compared with controls. These CD8+ expan sions were paralleled by expansions of CD8+ T cells bearing specific TcR V alpha/beta chains, namely V beta 5.2. Moreover, AHD, but not controls, carr ying the H63D mutation in the HFE gene showed significantly higher percenta ges of CD28- T cells within the CD8+ T-cell pool than AHD carrying the norm al HFE gene. Finally, high numbers of CD8+CD28- T cells in AHD were associa ted with lower levels of the liver-related enzymes ALT and GGT. Conclusions: This study showed that under active ethanol consumption, expan sions of discrete CD8+ T-cell subsets occur within the CD8+ T-cell pool, th at molecules of the MHC-class I locus seem to influence the extent of the e xpansions, and that high numbers of CD8+ CD28- T cells are associated with low levels of liver enzymes in AHD.