Spontaneous occurrence of autoimmune cholangitis in senescent mice

Abstract

The biliary lesions that developed spontaneously in senescent female C57BL/6NCrj mice were investigated. Degeneration of the bile duct epithelium was observed in 12 of 13 mice (92%), destruction of bile duct epithelial cells was seen in six of 13 mice (46%) and chronic non-suppurative destructive cholangitis was found in three of 13 mice (23%). The biliary lesions were characterized by prominent round cell infiltrates in the portal areas. Extra-hepatic lesions such as sialoadenitis were observed in six mice (46%) and pancreatis in seven (53%). IgM class antipyruvate dehydrogenase antibody was positive in one of three C57BL/6NCrj mice not given anti-Lyt 2 antibody and in three of six C57BL/6NCrj mice injected with anti-Lyt 2 antibody. These lesions were not observed in male C57BL/6NCrj mice, young female C57BL/6NCrj mice, or ICR mice. However, by transferring the splenic cells of senescent female C57BL/6NCrj mice to 6 week old females, the biliary lesions could be transferred at the rate of 6/9. The lymphocytes infiltrating in the bile ducts were CD8 positive lymphocytes. Moreover, in the ultrastructural immunocytochemical analysis of lymphocytes infiltrating bile duct epithelia, CD8 positive lymphocytes often formed broad contacts with the epithelial cells. The biliary lesions developing spontaneously in these mice are similar to those found in human primary biliary cirrhosis.