Quantitative and functional analysis of PDC-E2-specific autoreactive cytotoxic T lymphocytes in primary biliary cirrhosis

J Clin Invest. 2002 May;109(9):1231-40. doi: 10.1172/JCI14698.


While the pathologic mechanisms responsible for organ-specific tissue damage in primary biliary cirrhosis (PBC) remain an enigma, it has been suggested that the pathology is mediated by autoreactive T cells infiltrating the intrahepatic bile ducts. Previously, we have documented that there is 100-fold enrichment in the frequency of CD4(+) autoreactive T cells in the liver that are specific for peptides encoded by the E2 components of the pyruvate dehydrogenase complexes (PDC-E2). We have also recently characterized the first MHC class I-restricted epitope for PDC-E2, namely amino acid 159-167, a region very similar to the epitope recognized by MHC class II-restricted CD4(+) cells and by autoantibodies. The effector functions of these PDC-E2(159-167)-specific CD8(+) cytotoxic T lymphocytes (CTLs) are not well understood. We have taken advantage of tetramer technology and report herein that there is tenfold increase in the frequency of PDC-E2(159-167)-specific CTLs in the liver as compared with the blood in PBC. In addition, the precursor frequency of the CTLs in blood was significantly higher in early-stage PBC. Of interest was the fact that, upon stimulation with the peptide, the response of PDC-E2(159-167) tetramer-positive cells is heterogeneous with respect to IFN-gamma synthesis. These data, we believe for the first time, document the enrichment of autoantigen-specific CD8(+) T cells in the PBC liver, suggesting that CD8(+) T cells play a significant role in the immunopathogenesis of PBC.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Autoantigens / immunology*
  • Cells, Cultured
  • Dihydrolipoyllysine-Residue Acetyltransferase
  • Epitopes / immunology
  • Flow Cytometry
  • HLA-A Antigens / immunology
  • HLA-A2 Antigen
  • Humans
  • Interferon-gamma / biosynthesis
  • Liver / immunology
  • Liver Cirrhosis, Biliary / immunology*
  • Pyruvate Dehydrogenase Complex / immunology*
  • T-Lymphocytes, Cytotoxic / immunology*


  • Autoantigens
  • Epitopes
  • HLA-A Antigens
  • HLA-A*02:01 antigen
  • HLA-A2 Antigen
  • Pyruvate Dehydrogenase Complex
  • Interferon-gamma
  • Dihydrolipoyllysine-Residue Acetyltransferase