Induction and Maintenance of Anti-HBs in Immunosuppressed Rats After Liver Transplantation with HBsAg-pulsed Dendritic Cell Complex.

Abstract

This study aimed to investigate the efficacy of hepatitis B surface antigen (HBsAg)-pulsed dendritic cell (DC) complex in the induction and maintenance of anti-HBs in immunosuppressed rats after liver transplantation. Lewis-Brown Norway (BN) rat liver transplantation models were successfully established. Recipients were injected with tacrolimus (2 mg/Kg) daily post-operation for three months to maintain immunosuppression state; the recipients were then randomly divided into two groups: HBsAg-DC group (n=15) comprised rats intraperitoneally injected with HBsAg-DC complex at 14 and 28 d post-surgery and HBsAg group (n=15) comprised rats injected with HBsAg (200 μL) once a week for 12 weeks. Untreated rats post-transplantation were included in the control group (n=5). Histopathological changes were detected by light microscopy and transmission electron microscopy; mRNA expressions of IL-2 and IFN-γ in graft liver were analyzed through real-time polymerase chain reaction. Serum IL-2 and IFN-γ levels and anti-HB titer were detected through enzyme-linked immunosorbent assay. Changes in CD4+ and CD8+ T cells in the blood were detected through flow cytometry. IL-2 and IFN-γ expressions were lower in HBsAg-DC and HBsAg groups than in the control group (P<0.05). A high FK506 dose also induced a milder allograft rejection than the control dose. These findings showed that a high FK506 dose caused immunosuppression in rats after liver transplantation. A high anti-HB titer was detected in the HBsAg-DC group in one, two, and three months post-operation; by contrast, anti-HB titer was barely detected in the HBsAg group. High anti-HB titers could be induced and maintained in immunosuppressed rats; therefore, HBsAg-DC complex may prevent HBV reinfection after recipients undergo liver transplantation.