Expansions of CD8+CD28- and CD8+TcRVbeta5.2+ T cells in peripheral blood of heavy alcohol drinkers.
BACKGROUND
Despite heavy alcohol consumption, only a low percentage of heavy drinkers develop liver disease. Imbalances in T-cell subsets and iron metabolism parameters are common findings in heavy drinkers, yet the possible role played by discrete T-lymphocyte subsets under heavy alcohol consumption remains unclear.


METHODS
To gain new insights into the possible role played by T lymphocytes during alcohol consumption, characterization of CD28 expression and TcR repertoire 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 = 71) and a group of age-matched controls (n = 81), both HLA-phenotyped and HFE-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+CD28- expansions were paralleled by expansions of CD8+ T cells bearing specific TcR Valpha/beta chains, namely VP5.2. Moreover, AHD, but not controls, carrying the H63D mutation in the HFE gene showed significantly higher percentages of CD28- T cells within the CD8+ T-cell pool than AHD carrying the normal HFE gene. Finally, high numbers of CD8+CD28- T cells in AHD were associated with lower levels of the liver-related enzymes ALT and GGT.


CONCLUSIONS
This study showed that under active ethanol consumption, expansions of discrete CD8+ T-cell subsets occur within the CD8+ T-cell pool, that molecules of the MHC-class I locus seem to influence the extent of the expansions, and that high numbers of CD8+CD28- T cells are associated with low levels of liver enzymes in AHD.
Arosa
F A
FA
Laboratory of Molecular Immunology, Institute for Molecular and Cell Biology, Porto, Portugal. farosa@ibmc.up.pt
Porto
G
G
Cabeda
J M
JM
Lacerda
R
R
Resende
D
D
Cruz
E
E
Cardoso
C
C
Fonseca
M
M
Simões
C
C
Rodrigues
P
P
Bravo
F
F
Oliveira
J C
JC
Alves
H
H
Fraga
J
J
Justiça
B
B
de Sousa
M
M
D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000097:blood*; D000704:Analysis of Variance; D015415:Biomarkers; D018106:CD28 Antigens / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000378:metabolism*
D015415:Biomarkers; D018106:CD28 Antigens