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

Sheena M. Cruickshank, Jennifer Southgate, Peter J. Selby, Ludwik K. Trejdosiewicz*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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 antiinflammatory 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, ICAM1 (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, IFNγ and TNFα upregulated expression of ICAM-1, MHC class I and MHC class II, particularly in biliary epithelial cells. TGFβ 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. IFNγ 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.

Original languageEnglish
Pages (from-to)550-558
Number of pages9
JournalJournal of Hepatology
Issue number4
Publication statusPublished - 1 Oct 1998


  • Biliary
  • CD40
  • CD44
  • CD95
  • Cytokines
  • Epithelia
  • Immunoregulation

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