Induction and Maintenance of Anti-HBs in Immunosuppressed Rats After Liver Transplantation with HBsAg-pulsed Dendritic Cell Complex
Yakun Wu, Yiming Liu, Jianping Gong, Shengwei Li, Wei Zhang
Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China (mainland)
Ann Transplant 2015; 20:676-682
Available online: 2015-11-12
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.
MATERIAL AND METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
Keywords: Hepatitis B Antibodies, Hepatitis B virus, Immunosuppression, Liver Transplantation