BACKGROUND: Clinical and experimental studies have shown that an important deleterious consequence of excessive alcohol consumption is immunosuppression, specifically, a depletion in the mature CD4+ T-cell population. A predominant mechanism involved in T-cell depletion is activation-induced cell death (AICD). Although it is well documented that ethanol intake can cause depletion of CD4+ T cells, the mechanism of how alcohol mediates its effects is unclear. METHODS: The results were based on data from three separate experiments presented as mean +/- standard deviation (SD). Jurkat CD4+ T cells and peripheral blood lymphocytes were treated with 25 mM of ethanol (12-18 hr), followed by stimulation with mitogens Conconavalin A (5 microg/ml) and Phytohemmaglutinin (1 microg/ml) or T-cell receptor ligation (anti-CD3 antibody (5 microg/ml)) for 6 hr, and then harvested for measurement. The apoptotic cell death markers measured include cell viability, Caspase-3-like activity, and DNA fragmentation. RESULTS: We demonstrate that alcohol pretreatment enhances AICD of Jurkat CD4+ T cells and peripheral blood lymphocytes upon activation by CD3-crosslinking or stimulation with Conconavalin A and Phytohemmaglutinin. Furthermore, we find that the ethanol-mediated enhancement of T cells to apoptosis involves increased activation of Caspase-3 and can be abrogated by treatment with a specific inhibitor of Caspase-3. CONCLUSIONS: Our data indicate that ethanol can sensitize CD4+ T cells to enhanced stimulation-induced Caspase-3 activation and to subsequent AICD. This is, perhaps, an important mechanism in alcohol-induced immunosuppression.
BACKGROUND: Clinical and experimental studies have shown that an important deleterious consequence of excessive alcohol consumption is immunosuppression, specifically, a depletion in the mature CD4+ T-cell population. A predominant mechanism involved in T-cell depletion is activation-induced cell death (AICD). Although it is well documented that ethanol intake can cause depletion of CD4+ T cells, the mechanism of how alcohol mediates its effects is unclear. METHODS: The results were based on data from three separate experiments presented as mean +/- standard deviation (SD). Jurkat CD4+ T cells and peripheral blood lymphocytes were treated with 25 mM of ethanol (12-18 hr), followed by stimulation with mitogens Conconavalin A (5 microg/ml) and Phytohemmaglutinin (1 microg/ml) or T-cell receptor ligation (anti-CD3 antibody (5 microg/ml)) for 6 hr, and then harvested for measurement. The apoptotic cell death markers measured include cell viability, Caspase-3-like activity, and DNA fragmentation. RESULTS: We demonstrate that alcohol pretreatment enhances AICD of Jurkat CD4+ T cells and peripheral blood lymphocytes upon activation by CD3-crosslinking or stimulation with Conconavalin A and Phytohemmaglutinin. Furthermore, we find that the ethanol-mediated enhancement of T cells to apoptosis involves increased activation of Caspase-3 and can be abrogated by treatment with a specific inhibitor of Caspase-3. CONCLUSIONS: Our data indicate that ethanol can sensitize CD4+ T cells to enhanced stimulation-induced Caspase-3 activation and to subsequent AICD. This is, perhaps, an important mechanism in alcohol-induced immunosuppression.
Authors: Smita S Ghare; Swati Joshi-Barve; Akshata Moghe; Madhuvanti Patil; David F Barker; Leila Gobejishvili; Guy N Brock; Matthew Cave; Craig J McClain; Shirish S Barve Journal: J Immunol Date: 2014-06-04 Impact factor: 5.422
Authors: Emalie J Clement; Henry C-H Law; Fangfang Qiao; Dragana Noe; Jose G Trevino; Nicholas T Woods Journal: Cancers (Basel) Date: 2022-04-13 Impact factor: 6.639