Importance of Kupffer cells for T-cell-dependent liver injury in mice

T cells seem to be responsible for liver damage in any type of acute hepati tis. Nevertheless, the importance of Kupffer cells (KCs) for T-cell-depende nt liver failure is unclear. sere we focus on the role of KCs and tumor nec rosis factor (TNF) production after T cell stimulation in mice. T-cell- and TNF-dependent liver injury were induced either by Pseudomonas exotoxin A ( PEA), by concanavalin A (Con A), or by the combination of subtoxic doses of PEA and the superantigen Staphylococcus enterotoxin B (SEB), KCs were depl eted by clodronate liposomes, Although livers of PEA-treated mice contained foci of confluent necrosis and numerous apoptotic cells, hardly any apopto tic cells were observed in the livers of Con A-treated mice. Instead, large bridging necroses were visible. Elimination of KCs protected mice from PEA -, Con A-, or PEA/SEB-induced liver injury. In the absence of KCs, liver da mage was restricted to a few small necrotic areas. KCs were the main source of TNF. Hepatic TNF mRNA and protein production were strongly attenuated b ecause of KC-depletion whereas plasma TNF levels were unaltered. Our result s suggest that KCs play an Important role in T cell activation-induced live r injury by contributing TNF. Plasma TNF levels are poor diagnostic markers for the severity of TNF-dependent liver inflammation.