A new animal model of chronic autoimmune hepatitis mediated by the adaptive immune system

Progress in our understanding of autoimmune hepatitis (AIH) has been hampered by the lack of suitable animal models. Here we developed a strategy to break tolerance of a negatively selected, wild-type T cell repertoire by combining a self limited infection providing a danger signal together with modified liver self-antigens into mice. To this end we generated replication-deficient adenoviral constructs expressing common autoantigens of human AIH showing homology up to 80% with the murine proteins. Following a self-limited acute phase of liver destruction with elevated levels of transaminases we saw chronic evolv…