MUTUAL TOLERANCE AFTER LIVER AND NOT AFTER HEART-TRANSPLANTATION - EVALUATION OF PATIENT-ANTI-DONOR AND DONOR-ANTI-PATIENT RESPONSES BY MIXED LYMPHOCYTE CULTURE

The ultimate goal in organ transplantation is the induction of donor-s pecific transplantation tolerance. The fact that in some patients it i s possible to withdraw immunosuppressive therapy completely, suggests that immunological adaptation or donor-specific nonresponsiveness can occur following transplantation. In earlier studies we have shown that after blood transfusion, the mixed lymphocyte reactivity of the donor against patient peripheral blood mononuclear lymphocytes taken after blood transfusion gradually decreased with time. This may reflect the induction of an immunoregulatory mechanism, which protects the recipie nt against an immune reaction of the donor, enhancing a state of mixed chimerism. A similar phenomenon might also play a role in the immunol ogical mechanism leading to transplantation tolerance. Therefore, we s tudied responses in patients with a well-functioning liver and heart t ransplant using a primed lymphocyte test (PLT) and a mixed lymphocyte culture (MLC). Two years after liver transplantation the PLT and MLC r esponses of patient against donor were decreased significantly compare d to the situation before transplantation The response of donor agains t patient was also lower two years after transplantation The decreased responses were donor-specific since responses to third-party cells ge nerally remained unchanged. Tn heart transplant recipients we could no t detect a donor-specific downregulation. The reversed response, of do nor against patient, was not different from responses of third-party a gainst patient cells. Therefore, we conclude that donor-specific nonre sponsiveness is not induced in patients with well-functioning heart tr ansplants. In contrast, after a successful liver transplantation the r esponse of patient against donor is decreased, as is the reversed resp onse. It may be valuable to test whether in liver transplant patients withdrawing or reducing of maintenance immunosuppression is permitted for patients who appear to have developed two-way donor-specific hypor eactivity.