Ethanol-specific impairment of T-lymphocyte activation is caused by a transitory block in signal-transduction pathways.
BACKGROUND
Immune system derangement is characteristic of alcoholic liver cirrhosis. However, in vitro studies have never clarified the alcohol-induced T-lymphocyte dysfunction. The aim of this study was to examine any discrete phenotypical and functional abnormalities and possible impairment in transmembrane signal-transduction pathways that, if present on lymphocytes of patients with alcoholic cirrhosis, would also be reproducible after in vitro ethanol exposure of normal T cells.


METHODS
Lymphocytes from 25 patients were analyzed for their in vitro proliferative functions, intracellular Ca2+ fluxes, and inositol 1,4,5-triphosphate (IP3) generation. The same procedures were applied to normal T cells exposed in vitro to ethanol.


RESULTS
Lymphocytes failed to respond to anti-CD3 and anti-CD2 after in vitro stimulation, with decreased intracellular Ca2+ mobilization and IP3 generation but showed normal proliferative response to phytohemagglutinin. In vitro ethanol incubation of normal T lymphocytes resulted in rearrangement of the membrane CD45 antigen, favoring the expression of high-molecular-weight isoforms, and showed a poor blastogenic response to anti-CD3 and anti-CD2 with a decrease in intracellular Ca2+ mobilization and IP3 production. After a 6-month period of ethanol withdrawal, some patients had normalization of phenotypic and functional alterations.


CONCLUSIONS
The T-lymphocyte response to specific polyclonal activators may be severely impaired in alcohol abusers. However, it seems reversible after a period of controlled ethanol withdrawal.
Spinozzi
F
F
Department of Internal Medicine, School of Medicine, University of Perugia, Italy.
Agea
E
E
Bassotti
G
G
Belia
S
S
Rondoni
F
F
Broccucci
L
L
Solinas
A
A
Gerli
R
R
Bertotto
A
A
D000328:Adult; D000938:Antigen-Presenting Cells / Q000502:physiology; D015703:Antigens, CD / Q000502:physiology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D008108:Liver Diseases, Alcoholic / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D015398:Signal Transduction / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D015703:Antigens, CD; D007375:Interleukin-1; D007376:Interleukin-2; D000001:Calcimycin; D000431:Ethanol; D015544:Inositol 1,4,5-Trisphosphate; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium