Cutting edge: chronic inflammatory liver disease in mice expressing a CD28-specific ligand

Corse, Emily, Gottschalk, Rachel A., Park, Joon Seok, Sepulveda, Manuel A., Loke, P'ng, Sullivan, Timothy J., Johnson, Linda K., and Allison, James P. (2013) Cutting edge: chronic inflammatory liver disease in mice expressing a CD28-specific ligand. Journal of Immunology, 190 (2). pp. 526-530.

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Abstract

Inflammation of the normally tolerant liver microenvironment 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 disease with several pathologies found in AIH, including elevated serum aminotransferases in the context of normal alkaline phosphatase and bilirubin levels, lymphocytic inflammation, focal necrosis, oval cell hyperplasia, and fibrosis. The prevalence of IFN-ϓ-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 pathologies found in AIH.

Item ID: 29486
Item Type: Article (Research - C1)
ISSN: 1550-6606
Funders: Howard Hughes Medical Institute, National Institutes of Health
Date Deposited: 02 Oct 2013 23:50
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110706 Immunogenetics (incl Genetic Immunology) @ 60%
11 MEDICAL AND HEALTH SCIENCES > 1103 Clinical Sciences > 110316 Pathology (excl Oral Pathology) @ 40%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 100%
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