Regulatory T cells suppress in vitro proliferation of virus-specific CD8+ T cells during persistent hepatitis C virus infection
Rushbrook, S.M., Ward, S.M., Unitt, E., Vowler, S.L., Lucas, M., Klenerman, P. and Alexander, G.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.
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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.
|Publication Type:||Journal Article|
|Murdoch Affiliation:||Centre for Clinical Immunology and Biomedical Statistics|
|Publisher:||American Society for Microbiology|
|Copyright:||© 2005, American Society for Microbiology.|
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