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: 7852-7859. doi:10.1128/JVI.79.12.7852-7859.2005

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Author Rushbrook, Simon M.
Ward, Scott M.
Unitt, Esther
Vowler, Sarah L.
Lucas, Michaela
Klenerman, Paul
Alexander, Graeme J. M.
Title Regulatory T cells suppress in vitro proliferation of virus-specific CD8(+) T cells during persistent hepatitis C virus infection
Journal name Journal of Virology   Check publisher's open access policy
ISSN 0022-538X
1098-5514
Publication date 2005-06-01
Year available 2005
Sub-type Article (original research)
DOI 10.1128/JVI.79.12.7852-7859.2005
Open Access Status File (Publisher version)
Volume 79
Issue 12
Start page 7852
End page 7859
Total pages 8
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Language eng
Subject 060506 Virology
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 (T-reg) 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-gamma) frequency were analyzed with/without depletion of T-reg 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 perforin expression. Depletion of CD4(+)CD25(+) T-reg 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-gamma-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.
Keyword Virology
Growth-factor-beta
Peripheral-blood
Lymphocyte Response
Peptide Tetramers
Cd8+t Cells
Ex-vivo
Memory
Phenotype
Interleukin-10
Tolerance
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Medicine Publications
 
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Created: Fri, 25 Jan 2008, 16:34:31 EST