Cytomegalovirus infection and proinflammatory cytokine activation modulatethe surface immune determinant expression and immunogenicity of cultured murine extrahepatic bile duct epithelial cells

Murine extrahepatic bile duct epithelial cells (MEBEC) were isolated from e xtrahepatic bile ducts of BALB/c mice and established in primary culture. T he epithelial origin was confirmed by positive cytokeratin 19 staining for these cells and the presence of microvilli and tight junctions under electr on microscopy. By immunofluorescent staining with monoclonal antibodies and flow-cytometric analysis, MEBEC in culture constitutively express low leve ls of intercellular adhesion molecule (ICAM)-1, class I and class II major histocompatibility (MHC) antigens. The expression of ICAM-1 was significant ly increased by interferon gamma (INF-gamma) or tumour necrosis factor alph a (TNF-alpha) stimulation. Class I and class II antigen expression were sig nificantly enhanced by INF-gamma and in vitro murine cytomegalovirus (MCMV) infection. MEBEC infected with MCMV revealed a progressive cytopathic effe ct. MEBEC activated by INF-gamma or infected by MCMV induced a low but sign ificant proliferation of allogeneic T cells and displayed a significant dec rease in the absorbance at O.D. 550 nm in a microtitre tetrazolium assay af ter these treated cells were co-cultured with allogeneic T cells. These res ults suggest that following the up-regulation of surface MHC antigen and ad hesion molecule expression with cytokines or MCMV, the MEBEC can function a s antigen-presenting cells and initiate T-cell proliferation, which in turn trigger the recognition of MEBEC by effector T-cell-mediated cytotoxic res ponses. These findings may be implicated in the pathogenesis of virally ind uced, immune-mediated extrahepatic bile duct damage disorders.