Animal models of autoimmune hepatitis

Autoimmune hepatitis (AIH) is difficult to study in humans because of the late diagnosis, the heterogenic genetic background and the lack of tissue specimens. Therefore, animal models have been used for more than 90 years to study liver-specific immune regulation. This article summarizes how early studies of experimental AIH established the importance of T cells for causing the liver injury and how regulatory pathways were detected. Studies in transgenic models demonstrated that T cells can be tolerant to liver antigens by ignorance, deletion, anergy, and receptor downregulation. They furthermore defined functions in antigen presentation for hepatocytes and sinusoidal endothelial cells. Studies in cytokine-induced models show common effector cascades resulting from T-cell activation and the interaction of innate and adaptive immune response. The use of animal models of AIH will improve our understanding of the pathophysiology of the disease and might help to explore new possibilities for therapy and prevention.