Epitopes described in "T cells with a CD4+CD25+ regulatory phenotype suppress in vitro proliferation of virus-specific CD8+ T cells during chronic hepatitis C virus infection."

Article Authors:Tobias Boettler; Hans Christian Spangenberg; Christoph Neumann-Haefelin; Elisabeth Panther; Simonetta Urbani; Carlo Ferrari; Hubert E Blum; Fritz von Weizs├Ącker; Robert Thimme
Article Title:T cells with a CD4+CD25+ regulatory phenotype suppress in vitro proliferation of virus-specific CD8+ T cells during chronic hepatitis C virus infection.
Reference Detail
Reference ID:1001147
Abstract:Chronic hepatitis C virus (HCV) infection is associated with impaired proliferative, cytokine, and cytotoxic effector functions of HCV-specific CD8(+) T cells that probably contribute significantly to viral persistence. Here, we investigated the potential role of T cells with a CD4(+)CD25(+) regulatory phenotype in suppressing virus-specific CD8(+) T-cell proliferation during chronic HCV infection. In vitro depletion studies and coculture experiments revealed that peptide specific proliferation as well as gamma interferon production of HCV-specific CD8(+) T cells were inhibited by CD4(+)CD25(+) T cells. This inhibition was dose dependent, required direct cell-cell contact, and was independent of interleukin-10 and transforming growth factor beta. Interestingly, the T-cell-mediated suppression in chronically HCV-infected patients was not restricted to HCV-specific CD8(+) T cells but also to influenza virus-specific CD8(+) T cells. Importantly, CD4(+)CD25(+) T cells from persons recovered from HCV infection and from healthy blood donors exhibited significantly less suppressor activity. Thus, the inhibition of virus-specific CD8(+) T-cell proliferation was enhanced in chronically HCV-infected patients. This was associated with a higher frequency of circulating CD4(+)CD25(+) cells observed in this patient group. Taken together, our results suggest that chronic HCV infection leads to the expansion of CD4(+)CD25(+) T cells that are able to suppress CD8(+) T-cell responses to different viral antigens. Our results further suggest that CD4(+)CD25(+) T cells may contribute to viral persistence in chronically HCV-infected patients and may be a target for immunotherapy of chronic hepatitis C.
Affiliations:Department of Medicine II, University Hospital Freiburg, Hugstetter Strasse 55, D-79106 Freiburg, Germany.
Reference Type:Literature
PubMed ID:15919940
Journal:J Virol
Journal Volume:79
Article Pages:7860-7
Journal ISSN:1098-5514
Article Chemical List:Antigens, CD4;Receptors, Interleukin-2
Article MeSH List:Adult; Amino Acid Sequence; Antigens, CD4(metabolism); CD8-Positive T-Lymphocytes(immunology); Cell Communication; Female; Hepacivirus; Hepatitis C, Chronic(immunology); Humans; Lymphocyte Activation(immunology); Male; Middle Aged; Molecular Sequence Data; Phenotype; Receptors, Interleukin-2(metabolism); T-Lymphocytes, Regulatory(immunology)
Curation Last Updated:2015-11-25 20:01:19