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-specific transplantation tolerance. The fact that in some patients it is 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 recipient against an immune reaction of the donor, enhancing a state of mixed chimerism. A similar phenomenon might also play a role in the immunological mechanism leading to transplantation tolerance. Therefore, we studied responses in patients with a well-functioning liver and heart transplant using a primed lymphocyte test (PLT) and a mixed lymphocyte culture (MLC). Two years after liver transplantation the PLT and MLC responses of patient against donor were decreased significantly compared to the situation before transplantation. The response of donor against patient was also lower two years after transplantation. The decreased responses were donor-specific since responses to third-party cells generally remained unchanged. In heart transplant recipients we could not detect a donor-specific downregulation. The reversed response, of donor against patient, was not different from responses of third-party against patient cells. Therefore, we conclude that donor-specific nonresponsiveness is not induced in patients with well-functioning heart transplants. In contrast, after a successful liver transplantation the response of patient against donor is decreased, as is the reversed response. 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 hyporeactivity.

Comparison of T cell responses in patients with a long-term surviving renal allograft versus a long-term surviving liver allograft. It's a different world.

The aim of the present study was to analyze whether acquired transplantation tolerance had developed in patients with a long-term surviving renal or liver allograft. Analysis of antidonor cytotoxic T cell precursor frequencies was performed in 31 renal allograft recipients and 9 liver allograft recipients with good graft function 2 years after transplantation. The results demonstrated that, before transplantation, normal antidonor T cell responses were generated in both groups of patients. Two years after transplantation, donor-specific CTL nonresponsiveness had developed in a minority of the renal transplant recipients. In contrast, 8 out of 9 liver transplant recipients showed donor-specific mixed lymphocyte culture and CTL nonresponsiveness. These findings indicate that development of donor-specific T cell nonresponsiveness is not a common event after kidney transplantation, whereas liver transplantation seems to induce, at least in vitro, a state of donor-specific T cell nonresponsiveness.