DIFFUSE BILIARY-TRACT INVOLVEMENT MIMICKING PRIMARY SCLEROSING CHOLANGITIS IN AN EXPERIMENTAL-MODEL OF CHRONIC GRAFT-VERSUS-HOST DISEASE INMICE

Experimental graft-versus-host disease (GVHD) across minor histocompat ibility antigens was developed by injecting spleen and bone marrow cel ls (9 :1)of congenic B10.D2 mice into sublethally irradiated BALB/c mi ce, and the histologic features of the liver were studied for up to 14 months after transplantation. Both intrahepatic and extrahepatic bile ducts were severely involved in the GVHD process and showed features of non-suppurative cholangitis. Inflammatory cells, mainly lymphocytes , abutted the bile ducts and infiltrated into the duct epithelial laye r together with a variety of degenerative changes in the epithelial ce lls. The peak inflammatory activity occurred about 2-3 weeks after tra nsplantation. Thereafter, the inflammatory cell infiltration around th e bile ducts and in the bile duct epithelial layer gradually became re duced in severity, although the infiltration persisted during the enti re 14 month observation period. Periductal and duct wall fibroplasia b egan about 1 week after transplantation and gradually progressed. Afte r 23 months post-transplantation, distinct ductal and periductal fibro sis of both intrahepatic and extrahepatic bile ducts was observed. Thi s histologic feature resembled that of primary sclerosing cholangitis (PSC). These results suggest that PSC lesions might develop as a resul t of chronic cellular immunologic mechanisms in GVHD across minor hist ocompatibility barriers.