NONSUPPURATIVE CHOLANGITIS IS INDUCED IN NEONATALLY THYMECTOMIZED MICE - A POSSIBLE ANIMAL-MODEL FOR PRIMARY BILIARY-CIRRHOSIS

Neonatally thymectomized mice are unique in that they are prone to org an-specific autoimmune diseases. We investigated whether autoimmune ch olangitis could be induced in these mice when they were immunized with biliary antigens. Neonatally thymectomized A/J mice were immunized wi th 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 w ith 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 mononucle ar cells infiltrated around the bile duct in 14 of 22 mice, whereas li ttle or no accumulation was noted in other groups. Ultrastructural obs ervations revealed that the inflammatory cells consisted of lymphocyte s, plasma cells and macrophages. The bile duct showed degenerative cha nges and some lymphocytes infiltrated between bile duct epithelial cel ls. An immunohistochemical study showed that the accumulated lymphocyt es consisted of CD4(+) and CD8(+) T cells, as well as B cells. Both ma jor histocompatibility complex class I and class II antigens were expr essed on bile duct epithelial cells, Antimitochondrial antibody was de monstrated 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 blott ing. 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.