The efficiency of humoral immune transfer depends on both the graft and the immunosuppressive treatment.

The present study was designed to compare the efficiency of adoptive transfer of humoral immunity after liver, kidney, and heart transplantation in relation to the number of passenger lymphocytes, and to estimate the risk of a detrimental effect and the chance of a beneficial effect. Hepatitis B virus surface-antigen-vaccinated brown Norway rats (BNs) and AxC 9935 Irish (ACI rats) served as donors, and naïve Lewis (LEW) rats as recipients. The liver grafts contained 100 times more passenger lymphocytes than heart grafts, and the kidney grafts approximately ten times more, indicated by monoclonal CD45 antibody staining. Transient anti-HBs immunity did occur after transplantation of all three organ grafts. In all rejecting groups, the serum recipient-to-donor anti-HBs titer ratio (R/D ratio) was below 0.10%, with heart recipients showing half the level (0.05%) of liver recipients (0.09%). Under immunosuppression, R/D ratio doubled in liver or kidney recipients, but remained unaffected in heart recipients. Immune transfer was most efficient in immune-suppressed liver recipients in the spontaneously tolerant strain combination as indicated by a significantly higher R/D ratio (0.32%) and a longer titer persistence (up to 9 weeks) than in all other groups. Therefore, mainly liver and kidney graft recipients carry a risk, but also a chance of benefiting from the transfer of donor-derived immunity.

Adoptive transfer of HBV immunity by kidney transplantation and the effect of postoperative vaccination.

Transfer of hepatitis B immunity occurs upon the transfer of immunologically active cells from the donor to the recipient by means of an organ graft. This has been repeatedly demonstrated for bone marrow and liver transplantations. Evidence is now presented for the transfer of anti-hepatitis B surface antibodies (anti-HBs) after kidney transplantation in rats. Kidney donors from one syngeneic and two allogeneic rat strains were immunized twice with 4 microg of recombinant hepatitis B vaccine. In week 6 after the first vaccination, kidney grafts were transplanted into Lewis (LEW) rats. Half of the recipients underwent daily immunosuppressive treatment with cyclosporin A (CsA). All recipients were vaccinated either after 10 weeks or 1 week postoperatively. Anti-HBs titer was measured weekly. Effective anti-HBs titers (10-227 mIU/ml, lasting for 1-7 weeks) were detected in 86% (25/29) of recipient rats, whose corresponding donors all had a titer above 15,000 mIU/ml. Immunosuppression enhanced the donor-derived immunity in terms of recipient-to-donor titer ratio, maximal titer and titer persistence.

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.