Inhibition of T cell activation by normal human biliary epithelial cells

Background/Aims: Human intrahepatic biliary epithelial cells can express im mune recognition elements and are targets for immune attack in several live r pathologies. The aim of this study was to investigate the ability of bili ary epithelial cells to act as accessory cells for T cell activation in nor mal and inflammatory conditions. Methods: Normal biliary epithelial cells were cocultured with allogeneic un stimulated 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 phytohaemagg lutinin, mitogenic anti-CD3 antibody or recall antigen, irrespective of the presence of accessory cells. Biliary epithelial cells did not affect T cel l viability, promote or inhibit activation-induced apoptosis nor modulate e xpression of CD95/Fas. In presence of biliary epithelial cells, stimulated T cells failed to develop an antigen-committed (CD45R0(hi)) phenotype and w ere unresponsive to subsequent CD3 ligation, However, T cells underwent nor mal activation in the presence of biliary epithelial cells which had been p re-treated with Interferon gamma or TGF beta, 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.