The potential role of bone marrow transplantation in augmenting donor-derived immunity to hepatitis B after rat liver transplantation

Adoptive transfer of immunity to hepatitis B virus (HBV) is not provoked solely by bone marrow, but also by liver transplantation, although transiently. In the current study, simultaneous bone marrow transplantation, which possibly can increase the number of antibody-secreting cells, was performed to augment the efficacy of transferring HBV immunity. Stimulation of donor-derived immune cells by postoperative vaccination was used to investigate whether a secondary immune response can be induced in recipients. Orthotopic liver transplantation (n = 28), performed in three rat strain combinations representing different genetic constellations, was compared with bone marrow-augmented liver transplantation (n = 21). Donors had been vaccinated twice with recombinant hepatitis B surface antigen (HBsAg). Recipients surviving more than 10 weeks received a boost vaccination. All animals were monitored weekly for the presence of antibodies to HBsAg (anti-HBs). Effective anti-HBs titers were measured in 82% of liver recipients (23 of 28 recipients) and lasted from 2 to 9 weeks. Ninety percent of bone marrow-augmented liver recipients (19 of 21 recipients) seroconverted, with anti-HBs persisting from 2 to 12 weeks. A greater seroconversion rate, prolonged titer duration, and different pattern of titer development were observed in bone marrow-augmented liver recipients, although statistical significance could not be obtained because of the small numbers of comparable animals. Posttransplantation vaccination in recipients of combined grafts did not arouse a typical secondary antibody response, but showed a tendency toward an earlier and stronger response to vaccine in comparison to recipients without immune transfer. Simultaneous bone marrow transplantation showed an augmenting, but limited, effect on humoral immune transfer. Therefore, other potentially promising cellular strategies, such as transfer of in vivo and ex vivo stimulated antigen-specific cells should be pursued further. Improvement of the effect of postoperative vaccination possibly can be achieved by optimizing the immunization protocol.