{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T23:07:52Z","timestamp":1768000072094,"version":"3.49.0"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2011,1,1]],"date-time":"2011-01-01T00:00:00Z","timestamp":1293840000000},"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":[[2011,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>We previously described the NOD.c3c4 mouse, which is protected from type 1 diabetes (T1D) because of protective alleles at multiple insulin-dependent diabetes (Idd) genes, but develops autoimmune biliary disease (ABD) resembling primary biliary cirrhosis (PBC). In this paper, we characterize the NOD.ABD strain, which is genetically related to the NOD.c3c4 strain but develops both ABD and T1D. Histologically, NOD.ABD biliary disease is indistinguishable from that in NOD.c3c4 mice. The frequency of effector memory (CD44+CD62L\u2212) and central memory (CD44+CD62L+) CD8 T cells is significantly increased in the intrahepatic lymphocyte fraction of NOD.ABD mice, and NOD.ABD CD8 T cells produce more IFN-\u03b3 and TNF-\u03b1, compared with controls. NOD.ABD splenocytes can transfer ABD and T1D to NOD.c3c4 scid mice, but only T1D to NOD scid mice, suggesting that the genetic origin of the target organ and\/or its innate immune cells is critical to disease pathogenesis. The disease transfer model, importantly, shows that biliary duct damage (characteristic of PBC) and inflammation precede biliary epithelial cell proliferation. Unlike T1D where both CD4 and CD8 T cells are required for disease transfer, purified NOD.ABD CD8 T cells can transfer liver inflammation into NOD.c3c4 scid recipients, and disease transfer is ameliorated by cotransferring T regulatory cells. Unlike NOD.c3c4 mice, NOD.ABD mice do not develop anti-nuclear or anti-Smith autoantibodies; however, NOD.ABD mice do develop the antipyruvate dehydrogenase Abs typical of human PBC. The NOD.ABD strain is a model of immune dysregulation affecting two organ systems, most likely by mechanisms that do not completely coincide.<\/jats:p>","DOI":"10.4049\/jimmunol.1001597","type":"journal-article","created":{"date-parts":[[2010,12,18]],"date-time":"2010-12-18T04:50:06Z","timestamp":1292647806000},"page":"1259-1267","source":"Crossref","is-referenced-by-count":46,"title":["CD8 T Cells Mediate Direct Biliary Ductule Damage in Nonobese Diabetic Autoimmune Biliary Disease"],"prefix":"10.1093","volume":"186","author":[{"given":"Guo-Xiang","family":"Yang","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Allergy and Clinical Immunology, University of California , Davis, Davis, CA 95616"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuehong","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Immunology, Allergy and Rheumatology, University of Cincinnati College of Medicine , Cincinnati, OH 45267"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroki","family":"Tsukamoto","sequence":"additional","affiliation":[{"name":"Division of Immunology, Allergy and Rheumatology, University of Cincinnati College of Medicine , Cincinnati, OH 45267"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick S","family":"Leung","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Allergy and Clinical Immunology, University of California , Davis, Davis, CA 95616"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhe-Xiong","family":"Lian","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Allergy and Clinical Immunology, University of California , Davis, Davis, CA 95616"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel B","family":"Rainbow","sequence":"additional","affiliation":[{"name":"Juvenile Diabetes Research Foundation\/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge , Cambridge CB2 0XY ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kara M","family":"Hunter","sequence":"additional","affiliation":[{"name":"Juvenile Diabetes Research Foundation\/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge , Cambridge CB2 0XY ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerard A","family":"Morris","sequence":"additional","affiliation":[{"name":"Juvenile Diabetes Research Foundation\/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge , Cambridge CB2 0XY ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul A","family":"Lyons","sequence":"additional","affiliation":[{"name":"Juvenile Diabetes Research Foundation\/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge , Cambridge CB2 0XY ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurence B","family":"Peterson","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Merck Research Laboratories , Rahway, NJ 07065"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda S","family":"Wicker","sequence":"additional","affiliation":[{"name":"Juvenile Diabetes Research Foundation\/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge , Cambridge CB2 0XY ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M Eric","family":"Gershwin","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Allergy and Clinical Immunology, University of California , Davis, Davis, CA 95616"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William M","family":"Ridgway","sequence":"additional","affiliation":[{"name":"Division of Immunology, Allergy and Rheumatology, University of Cincinnati College of Medicine , Cincinnati, OH 45267"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2011,1,15]]},"reference":[{"key":"2025032410590326300_r1","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1034\/j.1600-0528.2002.017402.x","article-title":"Primary biliary cirrhosis: an orchestrated immune response against epithelial cells","volume":"174","author":"Gershwin","year":"2000","journal-title":"Immunol. 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Immunol."},{"key":"2025032410590326300_r4","first-page":"995","article-title":"T-cell responses to the components of pyruvate dehydrogenase complex in primary biliary cirrhosis","volume":"21","author":"Jones","year":"1995","journal-title":"Hepatology"},{"key":"2025032410590326300_r5","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.autrev.2004.04.001","article-title":"Is primary biliary cirrhosis a model autoimmune disease?","volume":"3","author":"Ichiki","year":"2004","journal-title":"Autoimmun. Rev."},{"key":"2025032410590326300_r6","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1172\/JCI0214698","article-title":"Quantitative and functional analysis of PDC-E2-specific autoreactive cytotoxic T lymphocytes in primary biliary cirrhosis","volume":"109","author":"Kita","year":"2002","journal-title":"J. Clin. 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Autoimmun."},{"key":"2025032410590326300_r12","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.jaut.2007.02.003","article-title":"The X and why of xenobiotics in primary biliary cirrhosis","volume":"28","author":"Rieger","year":"2007","journal-title":"J. Autoimmun."},{"key":"2025032410590326300_r13","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/S1089-3261(03)00102-8","article-title":"The epidemiology of primary biliary cirrhosis","volume":"7","author":"Prince","year":"2003","journal-title":"Clin. Liver Dis."},{"key":"2025032410590326300_r14","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1084\/jem.20051911","article-title":"NOD.c3c4 congenic mice develop autoimmune biliary disease that serologically and pathogenetically models human primary biliary cirrhosis","volume":"203","author":"Irie","year":"2006","journal-title":"J. Exp. 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Immunol."},{"key":"2025032410590326300_r16","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1002\/hep.21385","article-title":"IL-2 receptor \u03b1\u2212\/\u2212 mice and the development of primary biliary cirrhosis","volume":"44","author":"Wakabayashi","year":"2006","journal-title":"Hepatology"},{"key":"2025032410590326300_r17","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/S1074-7613(00)80170-3","article-title":"Abrogation of TGF\u03b2 signaling in T cells leads to spontaneous T cell differentiation and autoimmune disease","volume":"12","author":"Gorelik","year":"2000","journal-title":"Immunity"},{"key":"2025032410590326300_r18","doi-asserted-by":"crossref","first-page":"5075","DOI":"10.4049\/jimmunol.0903734","article-title":"Nonobese diabetic congenic strain analysis of autoimmune diabetes reveals genetic complexity of the Idd18 locus and identifies Vav3 as a candidate gene","volume":"184","author":"Fraser","year":"2010","journal-title":"J. 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Rare Dis."},{"key":"2025032410590326300_r26","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s00251-005-0066-1","article-title":"Genetic control of anti-Sm autoantibody production in NOD congenic mice narrowed to the Idd9.3 region","volume":"58","author":"Irie","year":"2006","journal-title":"Immunogenetics"},{"key":"2025032410590326300_r27","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1097\/MCG.0b013e3181c74e0d","article-title":"Concurrent autoimmune diseases in patients with autoimmune hepatitis","volume":"44","author":"Teufel","year":"2010","journal-title":"J. Clin. Gastroenterol."},{"key":"2025032410590326300_r28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1006\/jaut.1997.0170","article-title":"Combined analysis of GAD65 and ICA512(IA-2) autoantibodies in organ and non-organ-specific autoimmune diseases confers high specificity for insulin-dependent diabetes mellitus","volume":"11","author":"Pietropaolo","year":"1998","journal-title":"J. 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