Adoptive transfer of immunity to hepatitis B virus via kidney transplantation in the rat model
Patients with end stage renal disease as well as kidney transplantation recipients have a high risk of acquiring hepatitis B infection, but have a low response to active vaccination. Safe and effective means of preventing and treating hepatitis B are far from being satisfactory. Adoptive transfer of immunological active cells by bone marrow transplantation is a new approach in the therapy of HBV. This study aims to explore whether the immunity to hepatitis B virus (HBV) can be transferred from a donor to a recipient by transplantation of a kidney. Three strains of donors (Lewis, Brown Norway and ACI) were vaccinated with HBV vaccine prior to organ donation. Kidney grafts were transplanted orthotopically into Lewis recipients. Half of the animals were treated daily with CsA. Recipients underwent either late (POW 10) or early (POW1) vaccination to enhance donor derived immunity. Anti-HBs titer was measured weekly for a minimum of 14 postoperative weeks. Effective anti-HBs antibody titers were detected in 86% (25/29) of recipients and lasted for 1-7 (3.7 ± 1.6) weeks. High titer in donors led to a high anti-HBs response and a long persistence in the recipient. CsA treatment did not influence the titer development in the recipient adversely, but prolonged the maximal titer and its duration, which may be explained by the prolonged presence of plasma cells being protected from rejection. Response to postoperative vaccination in POW 10 was earlier and higher than even in naive recipients in 1/9 rat receiving a kidney graft from a vaccinated donor, suggesting an engraftment of donor derived cells. Several possible mechanisms of adoptive transfer of immunity to HBV via kidney transplantation are envisaged: 1). Passive transfer of donor antibodies remaining in the kidney graft. 2). Transfer of active antibody secreting cells within the passenger lymphocytes of the graft. 3). Engraftment of antibody producing donor derived cells. Clinical applications can be envisioned in the situation of living donation. Planned vaccination of the living kidney donor may contribute to reduce reactivation of hepatitis B or prevent de novo infection.