Analysis of T cell repertoire in the liver of patients with chronic hepatitis C

Clin Exp Immunol. 2000 Jul;121(1):120-6. doi: 10.1046/j.1365-2249.2000.01274.x.

Abstract

Many T cells infiltrate into the liver of patients with chronic hepatitis C (CH-C). They are believed to play a crucial role in the immunopathogenesis of hepatic inflammation, but their clonality and specificity are unknown. The aim of this study was to clarify the characteristics of these T cells. We analysed the complementarity-determining region (CDR)3 size lengths of T cell receptor (TCR) beta-chains by size spectratyping, and determined the sequences of Vbeta CDR3 after subcloning Vbeta-specific polymerase chain reaction products. Spectratyping showed clonal expansions in all liver specimens, most of which showed more than two T cell clones. Moreover, many non-clonal T cells also accumulated in the liver. Clonality of the T cells suspected by spectratyping was confirmed by CDR3 sequencing. Although the sequences revealed no whole CDR3-shared clones among different patients, some common motif sequences were observed. Our data suggest that T cells are stimulated by several hepatitis C virus (HCV) epitopes, then accumulate in the liver of CH-C patients. Shared motifs of expanded T cell clones suggest that they might recognize the same regions of HCV peptides, but have differences due to HCV peptide mutational changes. These clones might also interact with non-clonal T cells and play a crucial role in the immunopathogenesis of CH-C.

MeSH terms

  • Female
  • Hepatitis C, Chronic / genetics
  • Hepatitis C, Chronic / immunology*
  • Humans
  • Liver / cytology*
  • Male
  • Middle Aged
  • Receptors, Antigen, T-Cell, alpha-beta / classification
  • Receptors, Antigen, T-Cell, alpha-beta / genetics*
  • T-Lymphocytes / immunology*

Substances

  • Receptors, Antigen, T-Cell, alpha-beta