Intrahepatic and circulating HLA class II-restricted, hepatitis C virus-specific T cells: functional characterization in patients with chronic hepatitis C

Hepatology. 2002 May;35(5):1225-36. doi: 10.1053/jhep.2002.33153.

Abstract

To compare the functional features of circulating and intrahepatic hepatitis C virus (HCV)-specific CD4+ T cells in chronic HCV infection, peripheral blood and liver-infiltrating lymphocytes from 29 patients with chronic hepatitis C were stimulated with structural and nonstructural HCV proteins to produce antigen-specific T-cell lines and clones. Antigen specificity, fine specificity, phenotype, cytokine production, and T-cell receptor (TCR)-vbeta chain expression were analyzed. The results indicate a hierarchy of stimulatory capacity by the different HCV proteins, core being the antigen most frequently recognized by CD4+ intrahepatic lymphocytes, followed by NS4 and NS5. The CD4 response was directed simultaneously against different HCV proteins in individual patients, but fine-specificity analysis indicated that the response was generally focused on a limited number of immunodominant epitopes. Although the narrowly focused nature of this response may favor the emergence of escape mutations, this event was not observed by following-up over time the sequence of 2 epitopes strongly immunodominant for intrahepatic CD4 cells of a patient with chronic HCV infection. In conclusion, simultaneous analysis of peripheral blood and intrahepatic CD4 cells in the same patients indicated a predominant Th1 profile of HCV-specific CD4 cells and suggests a specific compartmentalization of virus-specific T cells into the liver.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / virology
  • Clone Cells
  • Cytokines / biosynthesis
  • Epitopes
  • Epitopes, T-Lymphocyte / genetics
  • Female
  • Genes, T-Cell Receptor beta / physiology
  • Hepacivirus / genetics
  • Hepacivirus / immunology*
  • Hepatitis C, Chronic / immunology
  • Hepatitis C, Chronic / virology*
  • Histocompatibility Antigens Class II / immunology*
  • Humans
  • Liver / immunology
  • Liver / virology
  • Male
  • Middle Aged
  • Mitogens / pharmacology
  • RNA, Viral / analysis

Substances

  • Cytokines
  • Epitopes
  • Epitopes, T-Lymphocyte
  • Histocompatibility Antigens Class II
  • Mitogens
  • RNA, Viral