Regulatory T Cells Suppress In Vitro Proliferation of Virus-Specific CD8+T Cells during Persistent Hepatitis C Virus Infection

Open Access
Publisher Website
Google Scholar
Abstract
The basis of chronic infection following exposure to hepatitis C virus (HCV) infection is unexplained. One factor may be the low frequency and immature phenotype of virus-specific CD8+T cells. The role of CD4+CD25+T regulatory (Treg) cells in priming and expanding virus-specific CD8+T cells was investigated. Twenty HLA-A2-positive patients with persistent HCV infection and 46 healthy controls were studied. Virus-specific CD8+T-cell proliferation and gamma interferon (IFN-γ) frequency were analyzed with/without depletion of Tregcells, using peptides derived from HCV, Epstein-Barr virus (EBV), and cytomegalovirus (CMV). CD4+CD25+Tregcells inhibited anti-CD3/CD28 CD8+T-cell proliferation and perforin expression. Depletion of CD4+CD25+Tregcells from chronic HCV patients in vitro increased HCV and EBV peptide-driven expansion (P= 0.0005 andP= 0.002, respectively) and also the number of HCV- and EBV-specific IFN-γ-expressing CD8+T cells. Although stimulated CD8+T cells expressed receptors for transforming growth factor beta and interleukin-10, the presence of antibody to transforming growth factor beta and interleukin-10 had no effect on the suppressive effect of CD4+CD25+regulatory T cells on CD8+T-cell proliferation. In conclusion, marked CD4+CD25+regulatory T-cell activity is present in patients with chronic HCV infection, which may contribute to weak HCV-specific CD8+T-cell responses and viral persistence.