<p>HBVsvp-Pulsed Dendritic Cell Immunotherapy Induces Th1 Polarization and Hepatitis B Virus-Specific Cytotoxic T Lymphocytes Production</p>

Abstract

Background: In chronic hepatitis B virus (CHB) patients, both dendritic cells (DCs) and T cells are functionally impaired and consequently the HBV-specific cellular immune responses are downregulated. The present study aims to investigate whether monocytederived DC (MoDCs)-pulsed-HBV subviral particles (HBVsvp) can polarize Th1 cells to induce HBV-specific cytotoxic T-lymphocytes (CTL) responses in CHB patients. Methods and Materials: To this end, the human hepatoma HepG2.2.15 cell line was used to produce HBVsvp as a culturing system, and HBVsvp were concentrated for highly virus titer using the polyethylene glycol protocol. Peripheral blood mononuclear cells (PBMCs), collected from CHB patients and healthy donors, were differentiated into MoDCs and T cells. PBMCs-derived MoDCs were first pulsed with HBVsvp and then cultured with PBMCsderived T cells. MoDCs and/or T subsets cells were identified for phenotypic activation by FACS analysis. The cytokine secretion of IL-4, IL-12, and IFN-γ in the culture supernatants was detected. Results: The MoDCs were restored for their activation upon pulsing with HBVsvp in vitro, as identified by significantly overexpression of both CD86 and HLA-DR, and overproduction of IL-4 and IL-12. Furthermore, MoDCs-pulsed-HBVsvp induced Th1 frequencies and activated HBV-specific CTL to produce significantly highest amount of IFN-γ. Enhanced HBV-specific CTL led to strong cytolytic capacity against HepG2.2.15. Conclusion: Overall, our data suggest that in vitro activation of MoDCs with HBVsvp overcomes the functionally impaired DCs and T cells in CHB patients offering a promising tool for therapeutic or vaccine-based approaches against HBV.

Dendritic cell‐based immunotherapy: A potential therapeutic option for chronic Hepatitis B virus infection

“…When DCs were loaded with subviral particles (HBVsvp) of HBV obtained from the HepG2.2.15 cell line, they were successfully activated with increased expression of MHC‐II, CD 86 as well as CCR‐7. After immunization with HBVsvp or HBsAg/HBcAg‐pulsed DCs, HBV‐specific immune reactions including anti‐HBs production, both HBsAg and HBcAg‐specific T cells were induced in mice 47–49 . Although vaccination of HBVsvp‐pulsed DCs activated with lipopolysaccharidestimulated a robust HBV‐specific antibody and T cell responses in HBV‐transgenic mice, neither expression of HBV antigens nor viral load were decreased 50 .…”