FAILURE OF IN-VITRO T-CELL ASSAYS TO PREDICT CLINICAL OUTCOME AFTER HUMAN KIDNEY-TRANSPLANTATION

Allotransplant rejection is a T-cell-dependent reaction. Functional in vitro T-cell assays are being used widely for donor-recipient matchin g in bone marrow transplantation and have recently been used in some c entres for transplant monitoring. In order to assess tolerance inducti on after clinical transplantation, we measured the T-cell response of the host against donor spleen cells of 33 kidney transplant patients b efore and every 3 months after transplantation over a period of 18 mon ths. The T-cell reactivity before transplantation was not significantl y different in any of the assays in rejecting and nonrejecting patient s. in the classical mixed lymphocyte culture (MLC), a donor-specific l oss of reactivity was seen only in a patient with a CMV-associated irr eversible transplant rejection. One patient with chronic rejection acq uired a very high MLC response against donor spleen cells and a high r esponse against third-party cells. Little or nonspecific changes were seen in the MLCs of all other patients. Using the method of limiting d ilution analysis (LDA), we found a significant reduction of donor-spec ific cytotoxic T-cell precursors (CTL-p) within the first 3 months aft er transplantation in most patients with high antidonor CTL-p frequenc ies before transplantation. The reduction of donor-specific CTL-p was seen in patients with rejection episodes as well as in patients withou t. Thus we conclude, in contrast to others, that MLC and CTL-p LDA hav e no predictive value on the outcome of clinical transplantation. (C) 1994 Wiley-Liss, Inc.