CD4 T lymphocytes cause hepatocyte apoptosis by releasing Th1 cytokines in cellular immunological liver injury.
OBJECTIVE
To investigate how lymphocytes induce hepatocyte apoptosis.


METHODS
Liver injury was elicited by the trinitrobenzenesulfonic acid (TNBS) in picryl chloride (PCI)-sensitized mice. An ear swelling was also triggered with TNBS to confirm its eliciting ability. An in vitro assay for inducing hepatocyte apoptosis was established.


RESULTS
TNBS significantly elicited liver injury as well as ear swelling in PCl-sensitized mice. In the liver injury, hepatocyte apoptosis was detected 6 h after TNBS treatment. Cyclosporin A inhibited both ear swelling and hepatocyte apoptosis. When spleen cells from PCl-sensitized mice were co-cultured for 24 h with those from normal mice that had been treated with TNBS for 20 min, the supernatant collected showed a strong apoptosis-inducing activity for hepatocytes. The apoptosis was significantly reduced when the spleen cells from PCl-sensitized mice were treated previously with anti-CD3 or anti-CD4 antibody. By treating the cells, galactosamine and cycloheximide also lowered the apoptosis-inducing activity and decreased TNF-alpha and IL-2 productions. However, galactosamine treatment of hepatocytes greatly facilitated their susceptibility to supernatant-induced apoptosis. By contrast, cycloheximide completely blocked the facilitation.


CONCLUSIONS
CD4+ T cells in mice with liver injury may cause hepatocyte apoptosis by releasing cytokines including TNF-alpha and IL-2.
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D056486:Chemical and Drug Induced Liver Injury; D016572:Cyclosporine / Q000494:pharmacology; D004427:Ear Diseases / Q000139:chemically induced; D004487:Edema / Q000139:chemically induced; D005260:Female; D022781:Hepatocytes / Q000502:physiology*; D007111:Immunity, Cellular; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007376:Interleukin-2 / Q000378:metabolism*; D008107:Liver Diseases / Q000276:immunology / Q000503:physiopathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010853:Picryl Chloride / Q000276:immunology; D014302:Trinitrobenzenesulfonic Acid; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D007166:Immunosuppressive Agents; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D016572:Cyclosporine; D014302:Trinitrobenzenesulfonic Acid; D010853:Picryl Chloride