5D). This resulted in an equal staging by blinded Ishak scoring (Fig. 5E) and in comparable sizes of hepatic infiltrates (data not shown). Moreover, T-cell responses against mFTCD were comparable in Ad-mFTCD mice (Fig. 5F) as compared to Ad-hFTCD mice (Fig. 4C). Taken together, molecular similarity was as effective as molecular identity in triggering emAIH. We next wanted to test if the newly developed model PCI32765 of emAIH was not only suited to investigate the pathophysiology of the disease but if it could also be used to develop new therapeutic strategies. To this end it was important to show that the disease can be successfully

treated with our current immunosuppressive standard therapies. Indeed, a single 8-week course of oral therapy with prednisolone was sufficient to substantially improve the hepatitis and 70% of investigated mice showed complete histological remission (Fig. 6). Recently, a prospective randomized trial has established budesonide as an alternative to prednisolone for induction of remission.[16] In fact budesonide was superior to prednisolone in inducing remission and patients treated with budesonide

had fewer steroid-related side effects. It was therefore reassuring that budesonide was as effective as prednisolone in treating murine hepatitis. As both standard immunosuppressive therapies PLX-4720 nmr were also effective in treating emAIH, we suggest that our model might also be suited to develop and test new therapeutic regimens for treatment MCE of AIH. We developed a model of

experimental murine autoimmune hepatitis closely resembling the human disease. Semi-blinded pathological analysis showed features suggestive of AIH such as lymphoplasmacellular infiltrates, interface hepatitis, and lobular inflammation. The disease was chronically evolving after initial priming, which is in sharp contrast to all animal models using liver-specific expression of a model antigen paired with T cells from T-cell receptor transgenic animals.[14, 17-19] In all such models hepatitis is rather short-lived and the outcome of the initial immune attack is usually tolerance. Even in double transgenic models suggesting a chronic hepatitis the liver-specific CD8+ T cells were rather hyporeactive and anergic.[14, 18] Nonetheless, some approaches result in massive lymphoid infiltrations as reasoned by the high precursor frequency of transgenic effector cells.[14, 19] Although these models were helpful in understanding tolerance mediated by the liver, they were not very helpful to study the pathophysiology of AIH or to develop new therapeutic concepts. Models of human disease with a polyspecific T-cell repertoire are, on the other hand, limited to identify exact cellular and molecular mechanisms, as the precursor frequency and affinity of autoreactive is usually low in this setting. AST and ALT were not elevated during the chronic phase of the emAIH.