Indirect action of tumor necrosis factor-alpha in liver injury during the CD8+ T cell response to an adeno-associated virus vector in mice

TNFalpha indirectly promotes liver damage and is not a direct hepatotoxic agent. IFNgamma also indirectly contributes to liver injury through Kupffer cell activation while, in parallel, directly promoting hepatitis through induction of hepatocyte major histocompatability complex class I. In principle, it may be possible to ameliorate this immunopathologic indirect mechanism by developing therapies that target Kupffer cells, without impairing CD8+ T-cell-mediated antiviral immunity. This would have great therapeutic potential in chronic viral hepatitis.