Histological changes of bile duct in experimental graft-versus-host disease across minor histocompatibility barriers. I. Light microscopic and immunocytochemical observations

Graft-versus-host disease (GVHD) across minor histocompatibility antigens was developed in mice and the bile duct lesions were surveyed for up to 7.5 months after spleen and bone marrow cell transplantation. Lymphoid cell infiltration was evident by day 3, reached maximum at 2 weeks, then reduced gradually and persisted during the observation period. Fibrous expansion of the portal tracts paralleled with the time after transplantation, but none of the cases progressed into liver cirrhosis. The infiltrates abutted the interlobular and septal bile ducts and distorted their appearance with a frequent infiltration of mononuclear lymphoid cells into the duct epithelial layer. The duct epithelium showed a variety of degenerative and hyperplastic changes, including nuclear enlargement with anisonucleosis, nuclear pyknosis, cytoplasmic and nuclear darkness, cytoplasmic vacuolization, focal epithelial dropout, formation of apoptotic bodies, and micropapillary infolding. Disappearance of the bile ducts and formation of granuloma around the bile ducts were not seen. Immunocytochemical study revealed the exclusive preponderance of helper/inducer T cells in the portal infiltrates and marked expression of I-A antigen on the bile duct epithelium in GVHD mice. These results suggest that immunological mechanisms by helper/inducer T cells against minor histocompatibility antigen on bile duct epithelium in association with class II molecules of MHC are important in the pathogenesis of the bile duct lesions. A putative role of such lymphocytes is discussed.