Induction of HCV-specific cell response in vitro by dendritic cells generated with interferon-α

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Abstract

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.

About the authors

E. R. Chernykh

Research Institute of Fundamental and Clinical Immunology

Email: ct_lab@mail.ru

Chernykh Elena Removna - RAS Corresponding Member, PhD, MD (Medicine), Professor, Head of the Laboratory of Cellular Immunotherapy, Research Institute of Fundamental and Clinical Immunology.

630099, Novosibirsk, Yadrintsevskaya str., 14.

Phone: +7 (383) 236-03-29. Fax: +7 (383) 222-70-28.

Russian Federation

E. A. Oleynik

Research Institute of Fundamental and Clinical Immunology

Email: oleynik-90@bk.ru

Oleynik Ekaterina Alexandrovna - Postgraduate Student, Laboratory of Cellular Immunotherapy, Research Institute of Fundamental and Clinical Immunology.

630099, Novosibirsk, Yadrintsevskaya str., 14.

Russian Federation

O. Yu. Leplina

Research Institute of Fundamental and Clinical Immunology

Email: oleplina@mail.ru

Leplina Olga Yur’evna - PhD, MD (Medicine), Leading Researcher, Laboratory of Cellular Immunotherapy, Research Institute of Fundamental and Clinical Immunology.

630099, Novosibirsk, Yadrintsevskaya str., 14.

Russian Federation

M. A. Tikhonova

Research Institute of Fundamental and Clinical Immunology

Email: martix-59@mail.ru

Tikhonova Marina Alexandrovna - PhD (Biology), Senior Researcher, Laboratory of Cellular Immunotherapy, Research Institute of Fundamental and Clinical Immunology.

630099, Novosibirsk, Yadrintsevskaya str., 14.

Russian Federation

T. V. Tyrinova

Research Institute of Fundamental and Clinical Immunology

Email: tyrinova@bk.ru

Tyrinova Tamara Viktorovna - PhD (Biology), Researcher, Laboratory of Cellular Immunotherapy, Research Institute of Fundamental and Clinical Immunology.

630099, Novosibirsk, Yadrintsevskaya str., 14.

Russian Federation

N. M. Starostina

Research Institute of Fundamental and Clinical Immunology

Email: ct_lab@mail.ru

Starostina Natalya Mihaylovna - Honored Doctor of Russian Federation, PhD (Medicine), Head of the Immunology Department, Clinics of Immunopathology, Research Institute of Fundamental and Clinical Immunology.

630099, Novosibirsk, Yadrintsevskaya str., 14.

Russian Federation

A. A. Ostanin

Research Institute of Fundamental and Clinical Immunology

Author for correspondence.
Email: ct_lab@mail.ru

Ostanin Alexander Anatolievich - PhD, MD (Medicine), Professor, Head Researcher, Laboratory of Cellular Immunotherapy, Research Institute of Fundamental and Clinical Immunology.

630099, Novosibirsk, Yadrintsevskaya str., 14.

Russian Federation

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Copyright (c) 2019 Chernykh E.R., Oleynik E.A., Leplina O.Y., Tikhonova M.A., Tyrinova T.V., Starostina N.M., Ostanin A.A.

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