ABSTRACT
Objective To study the effects of intra-bone marrow injection of donor bone marrow cells in combination with low dose radiation on the immunologic reaction of composite tissue allotransplantation.Methods The inbred SD rats were chosen as donors and inbred Wistar rats as recipients. Overall 40 recipients were classified into 4 groups randomly after allogeneic leg transplantation: group A received transplantation only; group B irradiation in the sublethal level (4.5 Gy?2 at a 4-h interval) and fludarabine (50 mg/kg, i.p.); group C, bone marrow cells were directly injected into the intra-bone marrow cavity of the recipients; group D, using a combination of the injection of fludarabine (50 mg/kg, i.p.), irradiation (4.5 Gy?2, at a 4-h interval) and injection of donor bone marrow cells. The rejection of grafts was observed. 120 days after induction of tolerance the mixed lymphocyte reaction (MIR) and skin grafting were examined to confirm tolerance status. To determine graft-versus-host disease (GVHD), rats in tolerance status were also histologically examined. Results As compared with other groups, mean rejection time and mean survival time of limb allografts were prolonged obviously in group D. Donor-specific tolerance was confirmed in all limb allograft recipients in group D by skin grafting and by MLR, and no signs of GVHD were also histologically examined. Conclusion Using a combination of injection of fludarabine, irradiation in the sublethal level and donor bone marrow cells, we have induced donor-specific immunological tolerance in allogeneic limb transplantation in rats without using any immnosuppressants after the operation.