By light and electron microscopic examinations, histologic changes in the liver of mice with graft-versus-host reaction (GVHR) were analyzed. To induce GVHR, C57BL/6 (B6) spleen cells were injected into (B6Xbm1)F1, (B6Xbm12)F1, and (bm1Xbm12)F1 mice. In (B6Xbm12)F1 recipient mice, bile duct changes resembling chronic non-suppurative destructive
cholangitis (CNSDC) and a formation of epithelioid
granulomas were observed during the course of GVHR. An epithelioid
granuloma in the liver of (B6Xbm1)F1 or (bm1.Xbm12)F1 recipients was not detected. By electron microscopy, the bile duct epithelia were seen to be in close contact with infiltrating cells, and marked alterations of their cytoplasm and microvilli were demonstrated; ie, vacuolation of the cytoplasm, deterioration of microvilli, and
bleb formation were frequently observed in the liver of class II-disparate hosts. Concerning the basement membrane, no marked changes characteristic of
primary biliary cirrhosis (PBC), such as many-layered basement membranes containing
osmium positive substance, were detected. Because the major histocompatibility complex (MHC) class II-disparate system was used in our experimental system in the GVHR, the
antigen expressed on the bile duct might be a target and be associated with the formation of the initial hepatic lesions in PBC such as CNSDC and epithelioid
granuloma formation. Thus, GVHR across the MHC
class II antigen is believed to play an important role in the development of PBC.