Activation of Th1 immunity is a common immune mechanism for the successful treatment of hepatitis B and C: tetramer assay and therapeutic implications

J Biomed Sci. 2003 Jan-Feb;10(1):120-35. doi: 10.1007/BF02256004.


Both chronic hepatitis B and C virus (HBV and HCV) infections respond ineffectively to current antiviral therapies. Recent studies have suggested that treatment outcomes may depend on the development of type 1 T helper (Th1) and Th2 cell responses. Specifically, activation of Th1 immunity may play a major role in successfully treating hepatitis B and C. This model was revisited herein by evaluating immune responses in 36 HBV and 40 HCV patients with or without treatment, in an attempt to find a common immune mechanism for successful treatment. The immune responses in all examined cases were studied by peripheral blood mononuclear cell (PBMC) proliferation and cytokine responses to viral antigens, cytotoxic T lymphocyte (CTL) responses, enzyme-linked immunospot (ELISPOT) assay, and tetramer staining of virus-specific CD8+ T cells. The overall results revealed that all responders among both HBV- and HCV-infected cases displayed significantly higher PBMC proliferation to viral antigens with a predominant Th1 cytokine profile. Furthermore, the Th1-dominant responses were associated with significant enhancement of CTL activities and were correlated with ELISPOT data, while non-responders responded more weakly. During therapy, the numbers of tetramer-staining, virus-specific CD8+ T cells showed greater increases in responders than in non-responders (p = 0.001). The frequencies determined by the tetramer assay were approximately 200-fold higher than data estimated by limiting-dilution analysis. In conclusion, activation of Th1 immunity accompanied by enhancement of CTL activity during therapy is a common immune mechanism for successfully treating hepatitis B and C, and therefore may have important therapeutic implications.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, Viral / immunology
  • Antiviral Agents / pharmacology*
  • CD8-Positive T-Lymphocytes / immunology
  • Cytokines / immunology
  • Epitopes / immunology
  • Female
  • Hepatitis B / drug therapy
  • Hepatitis B / immunology*
  • Hepatitis C / drug therapy
  • Hepatitis C / immunology*
  • Humans
  • Immunity, Cellular / drug effects*
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Male
  • Middle Aged
  • T-Lymphocytes, Cytotoxic / immunology
  • Th1 Cells / drug effects
  • Th1 Cells / immunology*
  • Th2 Cells / drug effects
  • Th2 Cells / immunology


  • Antigens, Viral
  • Antiviral Agents
  • Cytokines
  • Epitopes