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 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- and loaded with recombinant HCV proteins Core (1120) and NS3 (11921457) 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 (IFN)/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 IFN production. Similarly to donor DCs, DCCore/NS3 of patients with CHC induced a proliferative response in most cases (86%) and IFN 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--induced DCs for the prevention and treatment of chronic HCV infection.