Immunity to hepatitis B has been successfully transferred by bone marrow transplantation, but has also occurred after liver transplantation (LTx). This study was designed to analyse the influence of alloreactivity and immunosuppression, on the efficacy of adoptive immune transfer to hepatitis B by liver transplantation. Orthotopic LTx (n = 34) were performed in three rat strain combinations representing different genetic constellations. Donors had been vaccinated twice with recombinant hepatitis B surface antigen while recipients were unimmunized. Half of the allogeneic recipients were immunosuppressed with cyclosporin A. All animals were monitored weekly for the presence of anti-hepatitis B surface antibodies (anti-HBs). Effective anti-HBs titres were detected in 85% (29/34) of liver recipients and lasted from 2 to 10 weeks. Donor titre above >15 000 mIU/mL ensured a 100% seroconversion rate in the recipients. The maximal anti-HBs titre in recipients represented 0.06% approximately 0.76% of the donor titre. Rejection reduced the adoptive immune transfer, which was protected by immunosuppression. These observations suggest that transfer of functionally active donor lymphocytes, deriving from the graft, contributed to the donor-derived immune response in the recipient. Further studies to augment the donor-derived immune response are warranted to ensure a therapeutic effect for the recipient at risk of reinfection.
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 na 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.
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