Expression and cytokine regulation of immune recognition elements by normal human biliary epithelial and established liver cell lines in vitro

J Hepatol. 1998 Oct;29(4):550-8. doi: 10.1016/s0168-8278(98)80149-9.


Background/aims: Biliary epithelial cells are targets of immune-mediated attack in conditions such as primary biliary cirrhosis and allograft rejection. This has been attributed to the ability of biliary epithelial cells to express ligands for T cell receptors. We aimed to investigate the expression of immune recognition elements and the effects of pro-inflammatory and anti-inflammatory cytokines on cell surface phenotypes of normal human biliary epithelial cells and established human liver-derived (PLC/PRF/5, HepG2, Hep3B and CC-SW) lines.

Methods: Cells were cultured in the presence or absence of cytokines for 72 h, and expression of cell surface molecules was assessed by flow cytometry and immunofluorescence.

Results: All cell lines expressed MHC class I, ICAM-1 (CD54), LFA-3 (CD58) and EGF receptor, and all but Hep3B expressed Fas/Apo-1 (CD95). Unlike hepatocyte-derived cell lines, biliary epithelial cells and CC-SW expressed CD40 and CD44. As expected, IFNgamma and TNFalpha upregulated expression of ICAM-1, MHC class I and MHC class II, particularly in biliary epithelial cells. TGFbeta downregulated these molecules and downregulated CD95 on biliary epithelial cells, but upregulated LFA-3. The Th2 cytokines had little effect, although IL-4 upregulated CD95 expression on biliary epithelial cells. IFNgamma upregulated CD40 expression on biliary epithelial cells, CC-SW and HepG2.

Conclusions: These findings imply that biliary epithelial cells may be capable of interacting with activated T lymphocytes via CD40 and LFA-3, which are thought to be important T cell accessory ligands for T cell activation in a B7-independent manner. Sensitivity to pro-inflammatory cytokines and expression of CD95 may explain why biliary epithelial cells are primary targets for autoimmune attack.

MeSH terms

  • Bile Ducts, Intrahepatic / cytology
  • Bile Ducts, Intrahepatic / drug effects
  • Bile Ducts, Intrahepatic / immunology*
  • CD40 Antigens / analysis
  • Cell Line
  • Cytokines / pharmacology*
  • Epithelial Cells / immunology
  • Flow Cytometry
  • HLA-DR Antigens / analysis
  • Humans
  • Hyaluronan Receptors / analysis
  • Keratins / analysis
  • Liver / cytology
  • Liver / drug effects
  • Liver / immunology*


  • CD40 Antigens
  • Cytokines
  • HLA-DR Antigens
  • Hyaluronan Receptors
  • Keratins