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

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

S.M. Rushbrook, S.M. Ward, E. Unitt, S.L. Vowler, M. Lucas, P. Klenerman and G.J.M. Alexander
Journal of Virology, Vol.79(12), pp.7852-7859
2005
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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.

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Collaboration types
Domestic collaboration
Citation topics
1 Clinical & Life Sciences
1.125 Hepatitis
1.125.83 HCV
Web Of Science research areas
Virology
ESI research areas
Microbiology
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