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

• Published in: Journal of hepatology 2008-09, Vol.49 (3), p.329-338
• Main Authors: Burton, James R, Klarquist, Jared, Im, KyungAh, Smyk-Pearson, Sue, Golden-Mason, Lucy, Castelblanco, Nicole, Terrault, Norah, Rosen, Hugo R
• Format: Article
• Language: English
• Subjects: Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antiviral Agents - therapeutic use; Antiviral therapy; Biological and medical sciences; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD4-Positive T-Lymphocytes - pathology; Cohort Studies; Drug Therapy, Combination; Female; Forkhead Transcription Factors; Gastroenterology and Hepatology; Gastroenterology. Liver. Pancreas. Abdomen; Hepatitis C virus; Hepatitis C, Chronic - drug therapy; Hepatitis C, Chronic - immunology; Hepatitis C, Chronic - pathology; Humans; Interferon-alpha - therapeutic use; Interferon-gamma; Interferon-γ; Longitudinal Studies; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Polyethylene Glycols - therapeutic use; Prospective Studies; Recombinant Proteins; Ribavirin - therapeutic use; T cell immunity; T regulatory cells; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; T-Lymphocytes, Regulatory - pathology; Th1 Cells - immunology; Th1 Cells - metabolism; Th1 Cells - pathology; Treatment Outcome
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/j.jhep.2008.05.020

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-γ 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-γ 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.