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.
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.
Authors: D F Florescu; A M McCartney; F Qiu; A N Langnas; J Botha; D F Mercer; W Grant; A C Kalil Journal: Infection Date: 2011-11-29 Impact factor: 3.553
Authors: F Spinozzi; I Nicoletti; E Agea; S Belia; R Moraca; G Migliorati; C Riccardi; F Grignani; A Bertotto Journal: Immunology Date: 1995-11 Impact factor: 7.397
Authors: F Spinozzi; E Agea; O Bistoni; N Forenza; A Monaco; B Falini; G Bassotti; F De Benedictis; F Grignani; A Bertotto Journal: Mol Med Date: 1995-11 Impact factor: 6.354