IMPROVED RENAL-ALLOGRAFT SURVIVAL FOLLOWING DONOR-SPECIFIC TRANSFUSIONS .1. INDUCTION OF ANTIBODIES THAT INHIBIT PRIMARY ANTIDONOR MLC RESPONSE

  • 1 January 1985
    • journal article
    • research article
    • Vol. 39  (1) , 12-17
Abstract
A study was done to identify humoral factors induced by donor-specific transfusion (DST) plus azathioprine (AZA) that correlate with improved renal allograft survival (92% at 3-34 mo. posttransplantation) in a group of 24 DST patients. Plasma was obtained from patients prior to AZA and DST (to), 2-6 wk after the final transfusion but immediately prior to transplant (tt), and 6-12 wk 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 [mixed lymphocyte culture] with either patient to PBL [peripheral blood leukocytes] or unrelated control PBL used as responders. Patient tx plasma was uniformly inhibitory of MLC responses to donor and to pooled 3rd-party stimulators, regardless of the source of responding cells. The tx plasma inhibition was mediated by a nondialyzable factor, ruling out a direct drug effect. In contrast, the effect of tt plasma was less pronounced but more specific. In some patients, a strong reproducible inhibition of antidonor MLC by tt plasma was observed. However, other patients did not show this inhibitory effect; thus the inhibition was not statistically significant (1 > P > 0.05 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 2 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.