Inhibition of T cell activation by normal human biliary epithelial cells

Background/Aims: Human intrahepatic biliary epithelial cells can express immune recognition elements and are targets for immune attack in several liver pathologies. The aim of this study was to investigate the ability of biliary epithelial cells to act as accessory cells for T cell activation in normal and inflammatory conditions. Methods: Normal biliary epithelial cells were cocultured with allogeneic unstimulated and mitogen- or antigen-stimulated peripheral blood lymphocytes. T cell responses were assessed by flow cytometry. Results: Biliary epithelial cells did not induce allostimulation in resting T cells and inhibited T cell activation in response to either phytohaemagglutinin, mitogenic anti-CD3 antibody or recall antigen, irrespective of the presence of accessory cells. Biliary epithelial cells did not affect T cell viability, promote or inhibit activation-induced apoptosis nor modulate expression of CD95/Fas. In presence of biliary epithelial cells, stimulated T cells failed to develop an antigen-committed (CD45ROhi) phenotype and were unresponsive to subsequent CD3 ligation. However, T cells underwent normal activation in the presence of biliary epithelial cells which had been pre-treated with Interferon γ or TGFβ, cytokines implicated in liver disease. Conclusions: In normal liver, biliary epithelial cells inhibit rather than promote T cell activation, but their anergising effects may be overcome in response to trauma.