Immunotoxicology of T cell-dependent experimental liver injury

Microbial toxins as well as certain drugs and xenobiotics exert their toxic potential towards mammalian organisms by either activation or suppression of the immune system. We have investigated the immune stimulatory effect of either the bacterial superantigen staphylococcal enterotoxin B (SEB) or of the T cell activating anti-CD3 monoclonal antibody (alpha CD3-mAb) or of the T cell mitogenic plant lectin concanavalin A (Con A) in murine in vivo and in vitro systems. Any of these agents evoked a strong cytokine response in vitro and in vivo. Tumor necrosis factor-alpha (TNF) was identified as a common cytotoxic mediator which induced hepatocyte apoptosis as characterized by histological examination and internucleosomal DNA fragmentation, that preceded the release of liver specific enzymes into plasma and the histological appearance of necrosis. These mechanisms of acute liver failure observed under experimental conditions are discussed to account also for liver injury during acute episodes of autoimmune or viral hepatitis or rejection of liver grafts.