Prospective analysis of effector and regulatory CD4+ T cells in chronic HCV patients undergoing combination antiviral therapy

J Hepatol. 2008 Sep;49(3):329-38. doi: 10.1016/j.jhep.2008.05.020. Epub 2008 Jun 23.


Background/aims: The role of HCV-specific CD4(+) T cells and regulatory T cells in influencing the outcome of antiviral therapy is incompletely defined.

Methods: CD4(+) IFN-gamma ELISPOT assays (n=58) and flow cytometric analysis of FoxP3-expressing T regulatory cells (n=62) were performed on patients from the Virahep-C study at baseline, during and after cessation of antiviral therapy.

Results: Total HCV-specific IFN-gamma CD4(+) T cell ELISPOT responses did not increase with therapy, but rather decreased by 8 weeks and remained below baseline 24 weeks after cessation of therapy. There were no statistically significant differences with respect to viral kinetics, race and virologic outcome. In contrast, viral relapse after treatment was associated with a three-fold increase in HCV-specific responses. The frequency and phenotype of regulatory T cells during therapy were not significantly different in terms of race, viral kinetic groups or virologic outcome.

Conclusions: A contraction of HCV-specific CD4(+) T cell responses was found during treatment with recovery of responses in patients experiencing virologic relapse after treatment. The levels of FoxP3-expressing regulatory T cells did not vary by race and were not predictive of virologic outcome. Work is ongoing to explore the contribution of mechanisms independent of CD4(+) T cells in therapy-induced viral clearance.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Antiviral Agents / therapeutic use*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / pathology*
  • Cohort Studies
  • Drug Therapy, Combination
  • Female
  • Forkhead Transcription Factors
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / immunology
  • Hepatitis C, Chronic / pathology*
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use*
  • Interferon-gamma
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Polyethylene Glycols / therapeutic use*
  • Prospective Studies
  • Recombinant Proteins
  • Ribavirin / therapeutic use*
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism
  • T-Lymphocytes, Regulatory / pathology*
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th1 Cells / pathology
  • Treatment Outcome


  • Antiviral Agents
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • Polyethylene Glycols
  • Ribavirin
  • Interferon-gamma
  • peginterferon alfa-2a