ESTABLISHMENT AND IMMUNOLOGICAL CHARACTERIZATION OF CULTURED HUMAN GALLBLADDER EPITHELIAL-CELLS

Biliary epithelial cells are a primary site of damage in liver allogra ft rejection and in immunologically mediated diseases such as primary biliary cirrhosis. Human leukocyte antigens and adhesion molecules on the biliary epithelium are associated with T-lymphocytic binding, reco gnition and destruction. To investigate relevant cellular immunologica l mechanisms under standard conditions, we have established an in vitr o model using human gallbladder epithelial cells. Although not directl y affected in these aberrations, gallbladder epithelial cells are exce llent objects for immunological investigations. More than 10(8) highly purified cells were isolated and cultured longer than 6 wk in conflue nt monolayers. Cell growth was routinely established on uncoated plast ic culture dishes, and serum-free media could be applied for immunolog ical experiments. Cell characterization was performed by means of spec ific monoclonal antibodies typical for biliary epithelial cells. Cytok eratins 1 through 8, 18 and 19 and human epithelial cell antibody 125 always showed strong positive staining. Antigen patterns were examined before and after treatment with interferon-gamma by use of immunohist ochemical staining methods. Untreated human gallbladder epithelial cel ls expressed human leukocyte class I antigens but few or no class II a ntigens. After stimulation with interferon-gamma induction of human le ukocyte antigen-DR, -DP and -DQ was detected. In addition, intercellul ar adhesion molecule 1 was induced on these gallbladder epithelial cel ls. Therefore an immunological competence similar to that of biliary e pithelial cells could be demonstrated. In vitro cell cultures of gallb ladder epithelial cells offer a promising tool for subsequent investig ations concerning intrahepatic biliary epithelial cells and their inte ractions with cells of the immune System.