INDUCTION OF T-CELL IMMUNE RESPONSE IN CHRONIC HCV-INFECTED PATIENTS WITH UNDERLYING DENDRITIC CELL IMMUNOTHERAPY

A key role of T cells in viral elimination and absence of strong T cell responses in patients with chronic hepatitis C virus (HCV) infection presumes that activation of antigen-specific T cells may be a promising approach to enhance treatment efficacy. Given the central role of dendritic cells (DCs) in the induction of T cell response, the aim of our study was to evaluate effects of DC immunotherapy upon immunological parameters in chronic HCV infection. Ten patients with chronic hepatitis C (genotype 1) were vaccinated with monocytederived DCs, generated in presence of IFNα (IFN-DCs) and pulsed with recombinant HCV Core (1–120) and NS3 (1192–1457) proteins. The vaccination protocol included as initiating procedure (one injection per week, ns = 4) and maintaining treatment (one monthly injection, ns = 6), with subsequent follow up for 6 months. The immunotherapy was not associated with serious adverse events, significant post-vaccination reactions, or increased hepatitis C activity, according to biochemical tests. Ex vivo studies have shown that immunotherapy elicited strong and stable immune response to Core and moderate response to NS3 protein, which manifested as a significant increase of MNC proliferation and IFNγ production in response to Core and enhancement of IFNγ production (without higher proliferation rates), in response to NS3. DC immunotherapy also led to increase of ConA-induced MNC proliferation up to normal levels indicating a recovery of mitogenic T cell reactivity. Meanwhile, T cell activation did not elicit antigen-specific Th2 response and expansion of CD4+CD25+CD127 regulatory T cells. Despite induced immune response, the immunotherapy with DCs was not accompanied by decreased viremia levels. Nevertheless, a transitory decrease of viral load in four patients and stable decrease of viremia in two patients as well as an inverse correlation between NS3-specific proliferation and viremia (Rss = 0.62; p < 0.05) by the end of 6-month follow-up indicated that the antigenspecific T cells may have a potential to control viral replication.