Failure of in vitro T-cell assays to predict clinical outcome after human kidney transplantation

Abstract

Allotransplant rejection is a T‐cell‐dependent reaction. Functional in vitro T‐cell assays are being used widely for donorrecipient matching in bone marrow transplantation and have recently been used in some centres for transplant monitoring. In order to assess tolerance induction after clinical transplantation, we measured the T‐cell response of the host against donor spleen cells of 33 kidney transplant patients before and every 3 months after transplantation over a period of 18 months. The T‐cell reactivity before transplantation was not significantly different in any of the assays in rejecting and nonrejecting patients. In the classical mixed lymphocyte culture (MLC), a donor‐specific loss of reactivity was seen only in a patient with a CMV‐associated irreversible transplant rejection. One patient with chronic rejection acquired a very high MLC response against donor spleen cells and a high response against third‐party cells. Little or nonspecific changes were seen in the MLCs of all other patients. Using the method of limiting dilution analysis (LDA), we found a significant reduction of donor‐specific cytotoxic T‐cell precursors (CTL‐p) within the first 3 months after transplantation in most patients with high antidonor CTL‐p frequencies before transplantation. The reduction of donor‐specific CTL‐p was seen in patients with rejection episodes as well as in patients without. Thus we conclude, in contrast to others, that MLC and CTL‐p LDA have no predictive value on the outcome of clinical transplantation.