Induction of HCV-specific cell response in vitro by dendritic cells generated with interferon-α
The induction of a strong multi-epitope T-cell response against hepatitis C virus (HCV) plays an important role in eliminating the virus, whereas adoptive response deficiency contributes to chronic and rapid progression of HCV-infection. Since dendritic cells (DCs) are capable of priming naive T lym...
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Sankt-Peterburg : NIIÈM imeni Pastera
2019
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oai:doaj.org-article:0d0bcb113f96406fa1f0cc45c459bf902021-11-22T07:09:52ZInduction of HCV-specific cell response in vitro by dendritic cells generated with interferon-α2220-76192313-739810.15789/2220-7619-2019-1-76-86https://doaj.org/article/0d0bcb113f96406fa1f0cc45c459bf902019-05-01T00:00:00Zhttps://www.iimmun.ru/iimm/article/view/641https://doaj.org/toc/2220-7619https://doaj.org/toc/2313-7398The induction of a strong multi-epitope T-cell response against hepatitis C virus (HCV) plays an important role in eliminating the virus, whereas adoptive response deficiency contributes to chronic and rapid progression of HCV-infection. Since dendritic cells (DCs) are capable of priming naive T lymphocytes and induce an effective immune response, the use of DC-based vaccines to enhance the HCV-specific T cell response is considered as a new approach to treatment of chronic hepatitis C (CHC). The ability of DCs generated from monocytes in the presence of interferon-α and loaded with recombinant HCV proteins Core (1–120) and NS3 (1192–1457) to induce an antigen-specific cellular response in healthy donors and patients with CHC was investigated. The immune response was assessed by proliferative activity and Th1 (IFNγ)/Th2 (IL-4, IL-6) production in mononuclear cells (MNC) cultures, and activation of cytotoxic T-lymphocytes in the degranulation test. We demonstrated that the primary antigen-specific response in MNC cultures of seronegative donors was detected better by stimulation of DCs, loaded with both antigens (DCCore /NS3) than when loaded with a single protein. DCCore/NS3 induced the proliferative response and degranulation of CD8+ T cells in MNC cultures of all tested donors, and in 50% (5/10) cases — IFNγ production. Similarly to donor DCs, DCCore/NS3 of patients with CHC induced a proliferative response in most cases (86%) and IFNγ production in 57% cases. At the same time, the activation of cytotoxic T cells in patients was less frequent (patients vs donors 57 and 100%, respectively), which could be partly due to increased spontaneous degranulation of CD8+ T cells in some patients. The obtained data testify the possibility of using vaccines based on interferon-α-induced DCs for the prevention and treatment of chronic HCV infection.E. R. ChernykhE. A. OleynikO. Yu. LeplinaM. A. TikhonovaT. V. TyrinovaN. M. StarostinaA. A. OstaninSankt-Peterburg : NIIÈM imeni Pasteraarticlechronic hcv infectiont cell responsecore-antigenns3-antigendendritic cellsInfectious and parasitic diseasesRC109-216RUInfekciâ i Immunitet, Vol 9, Iss 1, Pp 76-86 (2019) |
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DOAJ |
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chronic hcv infection t cell response core-antigen ns3-antigen dendritic cells Infectious and parasitic diseases RC109-216 |
spellingShingle |
chronic hcv infection t cell response core-antigen ns3-antigen dendritic cells Infectious and parasitic diseases RC109-216 E. R. Chernykh E. A. Oleynik O. Yu. Leplina M. A. Tikhonova T. V. Tyrinova N. M. Starostina A. A. Ostanin Induction of HCV-specific cell response in vitro by dendritic cells generated with interferon-α |
description |
The induction of a strong multi-epitope T-cell response against hepatitis C virus (HCV) plays an important role in eliminating the virus, whereas adoptive response deficiency contributes to chronic and rapid progression of HCV-infection. Since dendritic cells (DCs) are capable of priming naive T lymphocytes and induce an effective immune response, the use of DC-based vaccines to enhance the HCV-specific T cell response is considered as a new approach to treatment of chronic hepatitis C (CHC). The ability of DCs generated from monocytes in the presence of interferon-α and loaded with recombinant HCV proteins Core (1–120) and NS3 (1192–1457) to induce an antigen-specific cellular response in healthy donors and patients with CHC was investigated. The immune response was assessed by proliferative activity and Th1 (IFNγ)/Th2 (IL-4, IL-6) production in mononuclear cells (MNC) cultures, and activation of cytotoxic T-lymphocytes in the degranulation test. We demonstrated that the primary antigen-specific response in MNC cultures of seronegative donors was detected better by stimulation of DCs, loaded with both antigens (DCCore /NS3) than when loaded with a single protein. DCCore/NS3 induced the proliferative response and degranulation of CD8+ T cells in MNC cultures of all tested donors, and in 50% (5/10) cases — IFNγ production. Similarly to donor DCs, DCCore/NS3 of patients with CHC induced a proliferative response in most cases (86%) and IFNγ production in 57% cases. At the same time, the activation of cytotoxic T cells in patients was less frequent (patients vs donors 57 and 100%, respectively), which could be partly due to increased spontaneous degranulation of CD8+ T cells in some patients. The obtained data testify the possibility of using vaccines based on interferon-α-induced DCs for the prevention and treatment of chronic HCV infection. |
format |
article |
author |
E. R. Chernykh E. A. Oleynik O. Yu. Leplina M. A. Tikhonova T. V. Tyrinova N. M. Starostina A. A. Ostanin |
author_facet |
E. R. Chernykh E. A. Oleynik O. Yu. Leplina M. A. Tikhonova T. V. Tyrinova N. M. Starostina A. A. Ostanin |
author_sort |
E. R. Chernykh |
title |
Induction of HCV-specific cell response in vitro by dendritic cells generated with interferon-α |
title_short |
Induction of HCV-specific cell response in vitro by dendritic cells generated with interferon-α |
title_full |
Induction of HCV-specific cell response in vitro by dendritic cells generated with interferon-α |
title_fullStr |
Induction of HCV-specific cell response in vitro by dendritic cells generated with interferon-α |
title_full_unstemmed |
Induction of HCV-specific cell response in vitro by dendritic cells generated with interferon-α |
title_sort |
induction of hcv-specific cell response in vitro by dendritic cells generated with interferon-α |
publisher |
Sankt-Peterburg : NIIÈM imeni Pastera |
publishDate |
2019 |
url |
https://doaj.org/article/0d0bcb113f96406fa1f0cc45c459bf90 |
work_keys_str_mv |
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_version_ |
1718417898836328448 |