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.

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