Improved renal allograft survival following donor-specific transfusions. I. Induction of antibodies that inhibit primary antidonor MLC response.

Our purpose was to identify humoral factors induced by donor-specific transfusion (DST) plus azathioprine (AZA) that correlate with improved renal allograft survival (92% at 3-34 months posttransplantation) in a group of 24 DST patients. Plasma was obtained from patients prior to AZA and DST (to), 2-6 weeks after the final transfusion but immediately prior to transplant (tt), and 6-12 weeks after renal transplantation and initiation of standard posttransplant immunosuppressive therapy (tx). Plasma was screened for inhibitory or stimulatory activity in a 6-day primary MLC, with either patient to PBL or unrelated control PBL used as responders. Patient tx plasma was uniformly inhibitory of MLC responses to donor and to pooled third-party stimulators, regardless of the source of responding cells. The tx plasma inhibition was mediated by a nondialysable factor, ruling out a direct drug effect. In contrast, the effect of tt plasma was less pronounced but more specific. In some patients, we observed a strong reproducible inhibition of antidonor MLC by tt plasma. However, other patients did not show this inhibitory effect; thus the inhibition was not statistically significant (1 greater than P greater than .05 by the Wilcoxon t test) when all patients were analyzed. Overall, patient tt plasma affected neither control antidonor MLC nor patient MLC responses to pooled allogenic stimulating cells. In two patients showing strong tt plasma inhibition of antidonor MLC, the inhibition appeared to be Ig-mediated. The results are discussed in relation to current theories of DST mechanisms.