Core-specific adaptive regulatory T-cells in different outcomes of hepatitis C
| Autor: | Natascha Vidovic, Tilman Sauerbruch, S. Arndt, Bettina Langhans, Ulrich Spengler, I. Braunschweiger, Wibke Schulte, Laura E. Layland, Johannes Oldenburg, Judith Satoguina, Achim Hoerauf |
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| Rok vydání: | 2010 |
| Předmět: |
Adult
Male Hepacivirus Hepatitis C virus Epitopes T-Lymphocyte chemical and pharmacologic phenomena Adaptive Immunity medicine.disease_cause T-Lymphocytes Regulatory Virus Epitope Immunophenotyping Antigen T-Lymphocyte Subsets medicine Immune Tolerance Humans IL-2 receptor Cells Cultured Aged Cell Proliferation biology hemic and immune systems General Medicine Hepatitis C Hepatitis C Chronic Middle Aged Viral Load medicine.disease biology.organism_classification Flow Cytometry Prognosis Virology Coculture Techniques Clone Cells Interleukin-10 Immunology Female Viral load |
| Zdroj: | Clinical science (London, England : 1979). 119(2) |
| ISSN: | 1470-8736 |
| Popis: | CD4+ Treg-cells (regulatory T-cells) probably contribute to the impaired virus-specific T-cell responses in chronic HCV (hepatitis C virus) infection; however, their antigen-specificity has remained elusive. In the present study, we analysed peripheral blood CD4+ Treg-cells in patients with chronic hepatitis C and subjects with self-limited HCV infection and characterized individual Treg-cell clones obtained from both groups at the phenotypic and functional level. Foxp3 (forkhead box p3)+CD25+CD4+ Treg-cells were detected more frequently in patients with chronic hepatitis C than self-limited HCV infection, which responded to HCV core stimulation and inhibited proliferation of reporter cells. Cloning under limiting dilution conditions resulted in 14 and six hypoproliferative Foxp3+CD25+CD127−CD4+ T-cell clones from patients with chronic hepatitis C and subjects with self-limited HCV infection respectively. All clones expressed Treg-cell markers and produced IL (interleukin)-10 upon mitogen stimulation. However, exclusively Treg-cell clones from chronic hepatitis C produced IL-10 in response to HCV core and inhibited proliferation of reporter T-cells. These core-specific Treg-cell clones recognized epitopes in two regions of HCV core (amino acids 1–44 and 79–113). Co-culture inhibition assays demonstrated Treg-cells to inhibit reporter T-cells via secretion of IL-10 and IL-35 rather than cell-contact-dependent mechanisms. Finally, the HCV-specific Treg-cell clones lost their functional capacity, along with Foxp3 expression, if kept in culture without HCV core exposure. In conclusion, we identified functionally active HCV core-specific Treg-cells in patients with chronic hepatitis C, which share their epitopes with conventional T-cells and require the continued presence of antigen to maintain their functional differentiation. Thus HCV core-specific Treg-cells may contribute to the immunoregulatory balance in chronic hepatitis C. |
| Databáze: | OpenAIRE |
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