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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Autores principales:	E. R. Chernykh, E. A. Oleynik, O. Yu. Leplina, M. A. Tikhonova, T. V. Tyrinova, N. M. Starostina, A. A. Ostanin
Formato:	article
Lenguaje:	RU
Publicado:	Sankt-Peterburg : NIIÈM imeni Pastera 2019
Materias:	chronic hcv infection t cell response core-antigen ns3-antigen dendritic cells Infectious and parasitic diseases RC109-216
Acceso en línea:	https://doaj.org/article/0d0bcb113f96406fa1f0cc45c459bf90
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spelling	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)
institution	DOAJ
collection	DOAJ
language	RU
topic	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
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Induction of HCV-specific cell response in vitro by dendritic cells generated with interferon-α

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