Nonsuppurative cholangitis is induced in neonatally thymectomized mice: A possible animal model for primary biliary cirrhosis

Abstract

Neonatally thymectomized mice are unique in that they are prone to organ-specific autoimmune diseases. We investigated whether autoimmune cholangitis could be induced in these mice when they were immunized with biliary antigens. Neonatally thymectomized A/J mice were immunized with porcine intrahepatic bile duct epithelial cells (group 1), porcine gallbladder epithelial cells (group 2), porcine splenocytes (group 3) or Freund's adjuvant (group 4). Nonthymectomized mice were immunized with bile duct epithelial cells (group 5) or Freund's adjuvant (group 6). The cell suspensions were injected intraperitoneally with Freund's adjuvant once a week for 8 wk. In group 1 varying amounts of mononuclear cells infiltrated around the bile duct in 14 of 22 mice, whereas little or no accumulation was noted in other groups. Ultrastructural observations revealed that the inflammatory cells consisted of lymphocytes, plasma cells and macrophages. The bile duct showed degenerative changes and some lymphocytes infiltrated between bile duct epithelial cells. An immunohistochemical study showed that the accumulated lymphocytes consisted of CD4+ and CD8+ T cells, as well as B cells. Both major histocompatibility complex class I and class II antigens were expressed on bile duct epithelial cells. Antimitochondrial antibody was demonstrated in some mice in groups 1 (9 of 17), 2 (2 of 3) and 5 (4 of 5) by immunofluorescence; the antibody reacted with the 68, 52 and 47 kD polypeptides of the pyruvate dehydrogenase complex on Western blotting. These findings suggest that autoimmune cholangitis can be induced in neonatally thymectomized mice stimulated with biliary antigens and that these mice could be a suitable animal model for primary biliary cirrhosis.