15919939

pubmed:Citation

12

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.

http://linkedlifedata.com/resource/pubmed/commentcorrection/15919939-10510089, http://linkedlifedata.com/resource/pubmed/commentcorrection/15919939-10553059, http://linkedlifedata.com/resource/pubmed/commentcorrection/15919939-10748236, http://linkedlifedata.com/resource/pubmed/commentcorrection/15919939-10790425, http://linkedlifedata.com/resource/pubmed/commentcorrection/15919939-10837065, http://linkedlifedata.com/resource/pubmed/commentcorrection/15919939-10850488, http://linkedlifedata.com/resource/pubmed/commentcorrection/15919939-10888927, http://linkedlifedata.com/resource/pubmed/commentcorrection/15919939-10895429, http://linkedlifedata.com/resource/pubmed/commentcorrection/15919939-11009080, http://linkedlifedata.com/resource/pubmed/commentcorrection/15919939-11356962, http://linkedlifedata.com/resource/pubmed/commentcorrection/15919939-11390436, http://linkedlifedata.com/resource/pubmed/commentcorrection/15919939-11439948, http://linkedlifedata.com/resource/pubmed/commentcorrection/15919939-11500822, http://linkedlifedata.com/resource/pubmed/commentcorrection/15919939-11754811, http://linkedlifedata.com/resource/pubmed/commentcorrection/15919939-11927944, http://linkedlifedata.com/resource/pubmed/commentcorrection/15919939-12081013, http://linkedlifedata.com/resource/pubmed/commentcorrection/15919939-12084927, http://linkedlifedata.com/resource/pubmed/commentcorrection/15919939-12217606, http://linkedlifedata.com/resource/pubmed/commentcorrection/15919939-12218168, http://linkedlifedata.com/resource/pubmed/commentcorrection/15919939-12407579, http://linkedlifedata.com/resource/pubmed/commentcorrection/15919939-12525661, http://linkedlifedata.com/resource/pubmed/commentcorrection/15919939-12527224, http://linkedlifedata.com/resource/pubmed/commentcorrection/15919939-12594515, http://linkedlifedata.com/resource/pubmed/commentcorrection/15919939-12655345, http://linkedlifedata.com/resource/pubmed/commentcorrection/15919939-12810686, http://linkedlifedata.com/resource/pubmed/commentcorrection/15919939-12974748, http://linkedlifedata.com/resource/pubmed/commentcorrection/15919939-14635058, http://linkedlifedata.com/resource/pubmed/commentcorrection/15919939-14647055, http://linkedlifedata.com/resource/pubmed/commentcorrection/15919939-14734757, http://linkedlifedata.com/resource/pubmed/commentcorrection/15919939-14963140, http://linkedlifedata.com/resource/pubmed/commentcorrection/15919939-15307180, http://linkedlifedata.com/resource/pubmed/commentcorrection/15919939-15486925, http://linkedlifedata.com/resource/pubmed/commentcorrection/15919939-15919940, http://linkedlifedata.com/resource/pubmed/commentcorrection/15919939-2136906, http://linkedlifedata.com/resource/pubmed/commentcorrection/15919939-8094901, http://linkedlifedata.com/resource/pubmed/commentcorrection/15919939-8676088, http://linkedlifedata.com/resource/pubmed/commentcorrection/15919939-8691133, http://linkedlifedata.com/resource/pubmed/commentcorrection/15919939-8810254, http://linkedlifedata.com/resource/pubmed/commentcorrection/15919939-8823309, http://linkedlifedata.com/resource/pubmed/commentcorrection/15919939-9049223, http://linkedlifedata.com/resource/pubmed/commentcorrection/15919939-9338786, http://linkedlifedata.com/resource/pubmed/commentcorrection/15919939-9914214

http://linkedlifedata.com/resource/pubmed/journal/0113724

http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD4, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-2

Jun

pubmed-author:AlexanderGraeme J MGJ, pubmed-author:KlenermanPaulP, pubmed-author:LucasMichaelaM, pubmed-author:RushbrookSimon MSM, pubmed-author:UnittEstherE, pubmed-author:VowlerSarah LSL, pubmed-author:WardScott MSM

79

Y

2009-11-18

2005

Peter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, South Parks Road, Oxford OX1 3SY, United Kingdom.