Immunogenicity of biliary epithelium: study of the adhesive interaction with lymphocytes.

Abstract

Intrahepatic bile ducts express a range of lymphocyte adhesion molecules during episodes of inflammation. This may contribute to the susceptibility of biliary epithelium to immunologic damage during liver allograft rejection, graft-versus-host disease, and primary biliary cirrhosis. However, no previous study has shown that these adhesion molecules are functional. The aim of this study was to define the molecular basis of lymphoepithelial interactions within the intrahepatic bile ducts. Human intrahepatic biliary epithelial cells (HIBECs) were cultured, and their interaction with resting and activated lymphocytes was studied using a flow-cytometric assay that allowed characterization of the adherent cells and functional investigation of individual adhesive interactions. The capacity of adherent cytotoxic lymphoid cells to damage HIBEC was studied using a standard 51Cr release assay. Allogeneic lymphocytes were bound by HIBECs; this adherence was increased by activation of either participating cell type. Cells with cytotoxic capacity were bound preferentially. At least 50% of the overall adhesion was dependent on lymphocyte function-associated antigen 1. Cytotoxicity assays showed that HIBECs were susceptible to lysis by lymphokine-activated natural killer cells. This study shows that the adhesion molecules expressed by HIBECs are functional and necessary for the activity of cytotoxic effector lymphocytes.