Regulatory T cells suppress in vitro proliferation of virus-specific CD8+ T cells during persistent hepatitis C virus infection

Rushbrook, Simon M., Ward, Scott M., Unitt, Esther, Vowler, Sarah L., Lucas, Michaela, Klenerman, Paul and Alexander, Graeme J.M. (2005) Regulatory T cells suppress in vitro proliferation of virus-specific CD8+ T cells during persistent hepatitis C virus infection. Journal of Virology, 79 (12). pp. 7852-7859. ISSN 0022-538X

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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 Treg cells, using peptides derived from HCV, Epstein-Barr virus (EBV), and cytomegalovirus (CMV). CD4+CD25+ T reg cells inhibited anti-CD3/CD28 CD8+ T-cell proliferation and perform expression. Depletion of CD4+CD25 + Treg cells from chronic HCV patients in vitro increased HCV and EBV peptide-driven expansion (P = 0.0005 and P = 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.

Item Type:	Article
Uncontrolled Keywords:	microbiology,immunology,insect science,virology,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/2400/2404
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
Related URLs:	https://www.scopus.com/pages/publication...
Depositing User:	LivePure Connector
Date Deposited:	30 Jun 2026 13:23
Last Modified:	05 Jul 2026 23:02
URI:	https://ueaeprints.uea.ac.uk/id/eprint/103532
DOI:	10.1128/JVI.79.12.7852-7859.2005

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