Prospective analysis of effector and regulatory CD4+ T cells in chronic HCV patients undergoing combination antiviral therapy☆
Received 28 December 2007; received in revised form 22 April 2008; accepted 7 May 2008. published online 25 June 2008.
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.
1University of Colorado Denver, School of Medicine, Division Gastroenterology & Hepatology, Hepatitis C Research Center, Aurora, CO, USA
2University of Pittsburgh, Graduate School of Public Health, Pittsburgh, PA, USA
3University of California – San Francisco, Division of Gastroenterology and Hepatology, San Francisco, CA, USA
Corresponding author. Present address: Waterman Professor of Medicine and Immunology, Division Head, Gastroenterology & Hepatology, GI & Hepatology Division, B-158 Academic Office Building 1, 12631 East 17th Avenue, Room 7614, P.O. Box 6511, Aurora, CO 80045, USA. Tel.: +1 303 724 1858; fax: +1 303 724 1891.
☆ Dr. Terrault receives honoraria and grant support from Roche Pharmaceuticals. No other authors have a potential conflict of interest to report . NIH funded study . This study was funded as a cooperative agreement by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) with co-support from the National Center on Minority Health and Health Disparities (NCMHD) and the Intramural Research Program of the National Cancer Institute (NCI) with further support under a Cooperative Research and Development Agreement (CRADA) with Roche Laboratories, Inc. Grant Nos: U01 DK60329, U01 DK60340, U01 DK 60324, U01 DK 60344, U01 DK60327, U01 DK 60335, U01 DK60352, U01DK 60342, U01 DK 60345, U01 DK 60309, U01 DK 60346, U01 DK 60349, U01 DK 60341. Other support: National Center for Research Resources (NCRR) General Clinical Research Centers Program Grants: M01 RR00645 (New York Presbyterian), M02 RR000079 (University of California, San Francisco), M01 RR 16500 (University of Maryland), M01 RR000042 (University of Michigan), M01 RR00046 (University of North Carolina).
ABSTRACT