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UBC Theses and Dissertations

Allograft enhancement in a rat heart transplant model : effect of T and B cell immunization Scudamore, Charles Henry


Acute and chronic rejection continue to be the most important problems in maintaining a functioning organ allograft. Despite advances in immunosuppression, organs are still damaged or destroyed by the recipient's immune system. In order to protect the transplanted organ it is necessary to overwhelm the host's immune system and thus expose the host to the complications of invasion from fungi, bacteria, protazoa, reduction in oncologic surveillance, and reduction of stem cell production. Donor specific immunosuppression would provide graft protection and allow maintenance of the host's immunologic competence. Graft enhancement has been described for many years. Current practice uses this principle by pretransfusing prospective kidney transplant recipients with type specific blood. Previous work has supported the concept that this clinical effort can be produced by certain cells in the blood, specifically, lymphocytes. To study the effects of preimmunization with T or B lymphocytes and platelets in a rat heterotopic heart transplant model, the following experiments were performed. Experiment 1: The effect of pretransplant immunization with lxlO7 donor specific T cells or B cells showed that T cells have little affect on rejection of heterotopic heart allograft and B cells caused prolongation of graft function. This effect is species specific and not due to a pure anti-idiotype phenomenon. Experiment 2: The effect of heating the purified T and B cells at 56°C for 30 minutes is known to denature the presenting protein antigens on the cell membranes without destroying the cell membrane. After pretransplant immunization, seven days prior to heterotopic heart transplant in the rat model, the previously observed prolongation of graft survival after nonheated B cell immunization was still present but not as marked. Experiment 4: The effect of pretransplant immunization of donor specific T and B cells treated by heating to 85°C for 10 minutes followed by heterotopic heart graft showed that there was a significant prolongation of the engrafted heart following immunization with the denatured B cells. Cellular proteins are denatured by this pretreatment but polysaccharides are not. Experiment 5: The effect of pretransplant immunization with purified donor specific platelets followed by heterotopic heart rat transplant showed no prolongation or shortening of graft survival. It is concluded that, in the heterotopic rat heart transplant model, immunization with purified T cells 7 days prior to transplant has little effect on rejection. When B cells are immunized in the same way, graft survival is prolonged. If the cells are heated to 56°C for 30 minutes this effect is reduced but not eliminated. This effect indicates that denaturation of protein HLA antigens on the presenting cell surface reduces the enhancing effect of the intact antigens on B cells. By denaturing, the presenting B cell protein graft enhancement is still present, suggesting the phenomenon of graft enhancement is not totally dependent on protein antigens but may have a contribution from mucopolysaccharides or other carbohydrates. Donor specific purified platelet pretransplant immunizations produced no statistically significant prolongation of either PV6 or F₁ heart grafts. This observation is consistent with the findings that purified T cell immunization do not produce graft enhancement.

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