Cutting Edge: Chronic Inflammatory Liver Disease in Mice Expressing a CD28-Specific Ligand.

Inflammation of the normally tolerant liver microen-vironment precedes the development of chronic liver disease. Study of the pathogenesis of autoimmune liver diseases, such as autoimmune hepatitis (AIH), has been hampered by a lack of autochthonous chronic animal models. Through our studies of T cell costimulation, we generated transgenic mice expressing a ligand specific for the CD28 receptor, which normally shares ligands with the related inhibitory receptor CTLA-4. The mice spontaneously develop chronic inflammatory liver dis-ease with several pathologies found in AIH, including elevated serum aminotransferases in the context of nor-mal alkaline phosphatase and bilirubin levels, lympho-cytic inflammation, focal necrosis, oval cell hyperplasia, and fibrosis. The prevalence of IFN-7--producing CD8+ T cells in the livers of transgenic mice suggests a role for autoimmune cytotoxicity in the chronic disease state. The CD28 ligand-specific transgenic mice will facilitate evaluation of CD8+ T cell function in liver disease pa-thologies found in AIH. [ABSTRACT FROM AUTHOR]