{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T03:00:18Z","timestamp":1774926018966,"version":"3.50.1"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2013,1,1]],"date-time":"2013-01-01T00:00:00Z","timestamp":1356998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>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-\u03b3\u2013producing CD8+ T cells in the livers of transgenic mice suggests a role for autoimmune cytotoxicity in the chronic disease state. The CD28 ligand\u2013specific transgenic mice will facilitate evaluation of CD8+ T cell function in liver disease pathologies found in AIH.<\/jats:p>","DOI":"10.4049\/jimmunol.1202621","type":"journal-article","created":{"date-parts":[[2012,12,18]],"date-time":"2012-12-18T05:16:01Z","timestamp":1355807761000},"page":"526-530","source":"Crossref","is-referenced-by-count":6,"title":["Cutting Edge: Chronic Inflammatory Liver Disease in Mice Expressing a CD28-Specific Ligand"],"prefix":"10.1093","volume":"190","author":[{"given":"Emily","family":"Corse","sequence":"first","affiliation":[{"name":"Program in Immunology, Howard Hughes Medical Institute, and Ludwig Center for Cancer Immunotherapy, Memorial Sloan-Kettering Cancer Center , New York, NY 10021"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel A","family":"Gottschalk","sequence":"additional","affiliation":[{"name":"Program in Immunology, Howard Hughes Medical Institute, and Ludwig Center for Cancer Immunotherapy, Memorial Sloan-Kettering Cancer Center , New York, NY 10021"},{"name":"Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences , New York, NY 10021"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joon Seok","family":"Park","sequence":"additional","affiliation":[{"name":"Program in Immunology, Howard Hughes Medical Institute, and Ludwig Center for Cancer Immunotherapy, Memorial Sloan-Kettering Cancer Center , New York, NY 10021"},{"name":"Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences , New York, NY 10021"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel A","family":"Sepulveda","sequence":"additional","affiliation":[{"name":"Program in Immunology, Howard Hughes Medical Institute, and Ludwig Center for Cancer Immunotherapy, Memorial Sloan-Kettering Cancer Center , New York, NY 10021"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P\u2019ng","family":"Loke","sequence":"additional","affiliation":[{"name":"Division of Immunology, Department of Molecular and Cell Biology, University of California , Berkeley, Berkeley, CA 94720"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy J","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Division of Immunology, Department of Molecular and Cell Biology, University of California , Berkeley, Berkeley, CA 94720"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda K","family":"Johnson","sequence":"additional","affiliation":[{"name":"Laboratory of Comparative Pathology, Memorial Sloan-Kettering Cancer Center , New York, NY 10021"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James P","family":"Allison","sequence":"additional","affiliation":[{"name":"Program in Immunology, Howard Hughes Medical Institute, and Ludwig Center for Cancer Immunotherapy, Memorial Sloan-Kettering Cancer Center , New York, NY 10021"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2013,1,15]]},"reference":[{"key":"2025032406253294800_r1","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/j.1600-065X.2009.00784.x","article-title":"Mechanisms of costimulation","volume":"229","author":"Sharpe","year":"2009","journal-title":"Immunol. Rev."},{"key":"2025032406253294800_r2","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1111\/j.1600-065X.2009.00775.x","article-title":"Regulating the regulators: costimulatory signals control the homeostasis and function of regulatory T cells","volume":"229","author":"Bour-Jordan","year":"2009","journal-title":"Immunol. Rev."},{"key":"2025032406253294800_r3","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1111\/j.1600-065X.2009.00763.x","article-title":"Negative regulators of T-cell activation: potential targets for therapeutic intervention in cancer, autoimmune disease, and persistent infections","volume":"229","author":"Pentcheva-Hoang","year":"2009","journal-title":"Immunol. Rev."},{"key":"2025032406253294800_r4","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1038\/nri3108","article-title":"The emerging role of CTLA4 as a cell-extrinsic regulator of T cell responses","volume":"11","author":"Walker","year":"2011","journal-title":"Nat. Rev. Immunol."},{"key":"2025032406253294800_r5","doi-asserted-by":"crossref","first-page":"2587","DOI":"10.1073\/pnas.051632398","article-title":"Lack of a role for transforming growth factor-beta in cytotoxic T lymphocyte antigen-4-mediated inhibition of T cell activation","volume":"98","author":"Sullivan","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032406253294800_r6","doi-asserted-by":"crossref","first-page":"2252","DOI":"10.1172\/JCI27856","article-title":"Inhibition of T cell activation and autoimmune diabetes using a B cell surface-linked CTLA-4 agonist","volume":"116","author":"Fife","year":"2006","journal-title":"J. Clin. Invest."},{"key":"2025032406253294800_r7","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1038\/nri2858","article-title":"Antigen-presenting cell function in the tolerogenic liver environment","volume":"10","author":"Thomson","year":"2010","journal-title":"Nat. Rev. Immunol."},{"key":"2025032406253294800_r8","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/nri981","article-title":"Hepatic T cells and liver tolerance","volume":"3","author":"Crispe","year":"2003","journal-title":"Nat. Rev. Immunol."},{"key":"2025032406253294800_r9","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1586\/egh.10.42","article-title":"Animal models of autoimmune hepatitis","volume":"4","author":"Czaja","year":"2010","journal-title":"Expert Rev. Gastroenterol. Hepatol."},{"key":"2025032406253294800_r10","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1159\/000329804","article-title":"Requirements and challenges of a preclinical autoimmune hepatitis mouse model","volume":"29","author":"Hardtke-Wolenski","year":"2011","journal-title":"Dig. Dis."},{"key":"2025032406253294800_r11","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1084\/jem.20071859","article-title":"Breaking tolerance to the natural human liver autoantigen cytochrome P450 2D6 by virus infection","volume":"205","author":"Holdener","year":"2008","journal-title":"J. Exp. Med."},{"key":"2025032406253294800_r12","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.ccr.2009.08.021","article-title":"A lymphotoxin-driven pathway to hepatocellular carcinoma","volume":"16","author":"Haybaeck","year":"2009","journal-title":"Cancer Cell"},{"key":"2025032406253294800_r13"},{"key":"2025032406253294800_r14","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1038\/nrgastro.2011.69","article-title":"Autoimmune hepatitis","volume":"8","author":"Mieli-Vergani","year":"2011","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"2025032406253294800_r15","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1002\/hep.21658","article-title":"Cytochrome P450IID6-specific CD8 T cell immune responses mirror disease activity in autoimmune hepatitis type 2","volume":"46","author":"Longhi","year":"2007","journal-title":"Hepatology"},{"key":"2025032406253294800_r16","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/S1074-7613(00)80333-7","article-title":"B7-1 and B7-2 have overlapping, critical roles in immunoglobulin class switching and germinal center formation","volume":"6","author":"Borriello","year":"1997","journal-title":"Immunity"},{"key":"2025032406253294800_r17","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1111\/j.1872-034X.2010.00757.x","article-title":"+49A\/G polymorphism of cytotoxic T-lymphocyte antigen 4 gene in type 1 autoimmune hepatitis and primary biliary cirrhosis: A meta-analysis","volume":"41","author":"Miyake","year":"2011","journal-title":"Hepatol. Res."},{"key":"2025032406253294800_r18","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/S0022-1759(00)00276-3","article-title":"A cassette vector for high-level reporter expression driven by a hybrid invariant chain promoter in transgenic mice","volume":"245","author":"van Santen","year":"2000","journal-title":"J. Immunol. Methods"},{"key":"2025032406253294800_r19","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1046\/j.1440-1711.1998.00709.x","article-title":"Defective TCR expression in transgenic mice constructed using cDNA-based alpha- and beta-chain genes under the control of heterologous regulatory elements","volume":"76","author":"Barnden","year":"1998","journal-title":"Immunol. Cell Biol."},{"key":"2025032406253294800_r20","doi-asserted-by":"crossref","first-page":"S15","DOI":"10.1038\/modpathol.3800684","article-title":"Autoimmune liver disease: overlap and outliers","volume":"20","author":"Washington","year":"2007","journal-title":"Mod. Pathol."},{"key":"2025032406253294800_r21","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1056\/NEJMra050408","article-title":"Autoimmune hepatitis","volume":"354","author":"Krawitt","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"2025032406253294800_r22","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1007\/s12072-010-9183-5","article-title":"Autoimmune hepatitis: new paradigms in the pathogenesis, diagnosis, and management","volume":"4","author":"Oo","year":"2010","journal-title":"Hepatol Int"},{"key":"2025032406253294800_r23","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1007\/s00535-012-0586-z","article-title":"Autoimmune hepatitis: a review","volume":"47","author":"Gossard","year":"2012","journal-title":"J. Gastroenterol."},{"key":"2025032406253294800_r24","doi-asserted-by":"crossref","first-page":"2193","DOI":"10.1002\/hep.23584","article-title":"Diagnosis and management of autoimmune hepatitis","volume":"51","author":"Manns","year":"2010","journal-title":"Hepatology"},{"key":"2025032406253294800_r25","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/S1074-7613(94)80016-2","article-title":"The liver eliminates T cells undergoing antigen-triggered apoptosis in vivo","volume":"1","author":"Huang","year":"1994","journal-title":"Immunity"},{"key":"2025032406253294800_r26","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1073\/pnas.91.2.614","article-title":"Chronic active hepatitis in transgenic mice expressing interferon-gamma in the liver","volume":"91","author":"Toyonaga","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032406253294800_r27","doi-asserted-by":"crossref","first-page":"6413","DOI":"10.4049\/jimmunol.166.10.6413","article-title":"Genetic regulation of autoimmune disease: BALB\/c background TGF-beta 1-deficient mice develop necroinflammatory IFN-gamma-dependent hepatitis","volume":"166","author":"Gorham","year":"2001","journal-title":"J. Immunol."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/190\/2\/526\/62500381\/1202621.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/190\/2\/526\/62500381\/1202621.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T01:11:50Z","timestamp":1742951510000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/190\/2\/526\/8001448"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,1]]},"references-count":27,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2013,1,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1202621","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2013,1]]},"published":{"date-parts":[[2013,1]]}}}