Autoimmune Cholangitis in the SJLJ Mouse is Antigen Non-specific英文文献资料.docVIP

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Autoimmune Cholangitis in the SJLJ Mouse is Antigen Non-specific英文文献资料.doc

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Autoimmune Cholangitis in the SJLJ Mouse is Antigen Non-specific英文文献资料

DevelopmentalImmunology,2002Vol.9(2),pp.103–111 AutoimmuneCholangitisintheSJL/JMouseisAntigen Non-speci?c MOTOKOSASAKIa,b,JORGEALLINAc,JOSEPHA.ODINc,SWANN.THUNGd,ROSSCOPPELe,YASUNINAKANUMAband M.ERICGERSHWINa,* aDivisionofRheumatology,AllergyandClinicalImmunology,UniversityofCaliforniaSchoolofMedicine,Davis,CA95616,USA; bDepartmentof HumanPathology,KanazawaUniversityGraduateSchoolofMedicine,Kanazawa,Japan;cDivisionofLiverDiseases,MountSinaiSchoolofMedicine, NewYork,NY10029,USA; dDepartmentofPathology,MountSinaiSchoolofMedicine,NewYork,NY10029,USA; eDepartmentofMicrobiology, MonashUniversity,Clayton,Vic.3168,Australia Primary biliary cirrhosis (PBC) is an autoimmune disease characterized by intrahepatic bile duct destruction and the production of anti-mitochondrial antibodies (AMA). The absence of an animal modelhasbeenastrikingimpedanceinde?ningthemolecularbasisofdisease.Previousworkhas suggestedthatSJL/Jmiceimmunizewiththepyruvatedehydrogenasecomplex(PDC-E2),themajor mitochondrialautoantigenofPBC,leadstothedevelopmentoflymphoidcellin?ltrationinportaltracts andamodelsystemcoinedautoimmunecholangitis.Wehypothesizedthatthispathologywouldbe augmentedifimmunizationoccurredinthepresenceofIFN-ginjections.Accordingly,SJL/Jmicewere immunizedwithPDC-E2and,forpurposeofcontrol,a-casein.Subgroupsofmicewerealsotreated withexogenousIFN-g.Asexpected,miceimmunizedwithPDC-E2,withorwithoutIFN-g ,developed hightiter AMAs.In contrast, mice immunized with a-casein, develop antinuclear antibodies. More importantly,theliversfrommiceimmunizedwithPDC-E2and/orthoseimmunizedwitha-caseinall displayedlymphoidcellin?ltrationtotheportaltracts,irrespectiveofbileductsize.Indeed,therewas nosigni?cantdifferencebetweentheexperimentalandthecontrolgroupsbyhistologicanalysis.Thus, autoimmunecholangitisinthesemiceisantigennon-speci?c. Keywords: Anti-mitochondrialantibody;Autoimmunity;Cholangitis;Liver;Primarybiliarycirrhosis; SJL/Jmice INTRODUCTION most likely develops as a multi-h