Improved renal allograft survival following donor-specific transfusions. II. In vitro correlates of early (DST-type) rejection episodes.

Early graft rejection crises in renal transplant patients pretreated with donor-specific transfusions (DST) have been attributed to an antibody-mediated reaction, or an in situ primed lymphocyte test (PLT) reaction in the grafted kidney resulting from priming of recipient T cells. To test these hypotheses, we analyzed the mixed lymphocyte culture (MLC) response to donor stimulator cells in 18 DST + azathioprine (AZA)-treated patients, including 7 with living-nonrelated donors (2 HLA-haplotype mismatch) and 11 with living-related donors (1 HLA-haplotype mismatch). Studies of the kinetics of anti-donor MLC responses of PBL obtained from patients before and after DST + AZA treatment revealed shifts in the magnitude and timing of antidonor MLC response. We found an increased peak MLC response to donor and/or third-party in 6/18 patients, 4 of whom had early rejection crises; the other 2 patients had blocking factors in their post-DST plasma that strongly (57-71%) inhibited their MLC response. Plasma factors were implicated in the mechanism of early graft crisis, in that patients with an enhanced MLC response in the presence of post-DST plasma showed a significantly (P less than .02) shorter time to first rejection episodes as compared with patients with plasma blocking factors. Finally, we confirmed the findings of others that a significant proportion (7/18) of DST + AZA-treated patients had a decreased MLC response. Although such patients experienced classic (2nd week or later) rejection episodes, none had a DST-type (less than or equal to 3 day) crisis. Our data supports the concept of T cell priming by DST, and suggests that patients who fail to develop concomitant suppressor cells or humoral blocking factors will develop a rapid onset cellular rejection crisis in the transplanted kidney.