Autoimmune cholangitis in the SJL/J mouse is antigen non-specific.
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 model has been a striking impedance in defining the molecular basis of disease. Previous work has suggested that SJL/J mice immunize with the pyruvate dehydrogenase complex (PDC-E2), the major mitochondrial autoantigen of PBC, leads to the development of lymphoid cell infiltration in portal tracts and a model system coined autoimmune cholangitis. We hypothesized that this pathology would be augmented if immunization occurred in the presence of IFN-gamma injections. Accordingly, SJL/J mice were immunized with PDC-E2 and, for purpose of control, alpha-casein. Subgroups of mice were also treated with exogenous IFN-gamma. As expected, mice immunized with PDC-E2, with or without IFN-gamma, developed high titer AMAs. In contrast, mice immunized with alpha-casein, develop antinuclear antibodies. More importantly, the livers from mice immunized with PDC-E2 and/or those immunized with alpha-casein all displayed lymphoid cell infiltration to the portal tracts, irrespective of bile duct size. Indeed, there was no significant difference between the experimental and the control groups by histologic analysis. Thus, autoimmune cholangitis in these mice is antigen non-specific.
Sasaki
Motoko
M
Division of Rheumatology, Allergy and Clinical Immunology, University of California School of Medicine, Davis, CA 95616, USA.
Allina
Jorge
J
Odin
Joseph A
JA
Thung
Swan N
SN
Coppel
Ross
R
Nakanuma
Yasuni
Y
Gershwin
M Eric
ME
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D001324:Autoantigens / Q000008:administration & dosage; D001327:Autoimmune Diseases / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000473:pathology; D002761:Cholangitis / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D002908:Chronic Disease; D004195:Disease Models, Animal; D005620:Freund's Adjuvant / Q000008:administration & dosage; D007114:Immunization; D007371:Interferon-gamma / Q000008:administration & dosage; D008105:Liver Cirrhosis, Biliary / Q000209:etiology / Q000276:immunology / Q000473:pathology; D051379:Mice; D008928:Mitochondria / Q000201:enzymology / Q000276:immunology; D011768:Pyruvate Dehydrogenase Complex / Q000008:administration & dosage / Q000276:immunology; D011994:Recombinant Proteins
D000276:Adjuvants, Immunologic; D001323:Autoantibodies; D001324:Autoantigens; D011768:Pyruvate Dehydrogenase Complex; D011994:Recombinant Proteins; D007371:Interferon-gamma; D005620:Freund's Adjuvant