THE INFLUENCE OF DONOR-SPECIFIC VERTEBRAL BODY DERIVED BONE-MARROW CELL INFUSION ON CANINE ISLET ALLOGRAFT SURVIVAL WITHOUT IRRADIATION CONDITIONING OF THE RECIPIENT

In recent studies in rodents, it was shown, that donor specific tolera nce towards islet allografts without irradiation therapy of the recipi ent is induced by bone marrow cell infusion in combination with tempor ary immunosuppression. In the present study, the effect of donor speci fic bone marrow cell (DBMC) infusion at the time of intrahepatic islet allotransplantation without irradiation conditioning of the recipient was investigated in the canine model, paralleling ongoing clinical tr ials. It was observed, that unfractionated bone marrow cells given sim ultaneous to islet allografts led to higher frequencies of rejection p eriods and decreased islet allograft survival, when administered to re cipients immunosuppressed with Cyclosporine A only. In contrast, an ad ditional short inductive treatment of the recipient with an anti-dog-T -lymphocyte monoclonal antibody (5G2) abrogated the enhanced immunogen icity of the unfractionated bone marrow preparation, prolonging islet allograft survival with no rejection episodes observed during the immu nosuppressive treatment with Cyclosporine. The composition of bone mar row cells might have contributed to the higher immunogenicity, since t he percentage of MHC-class II antigen bearing cells is similar to man, but significantly higher than compared to rodents. It is therefore su ggested, that further studies should encompass both timing of bone mar row cell infusion, appropriate immunosuppression and strategies to fun ctionally inactivate mature MHC-class-II positive cells prior to DBMC infusion.