Peripheral donor leukocytes prolong survival of rat renal allografts

Background. The development of strategies to enhance the survival of transp lanted organs and to potentially lower or even discontinue immunosuppressiv e therapy would represent a significant advancement in post-transplant pati ent care. Methods. We studied the effect of pretransplant infusion of donor leukocyte s alone or in combination with a short course of cyclosporine on the long-t erm outcome of a rat model of kidney allograft. Results. A single intravenous infusion of donor peripheral blood leukocytes (100 x 10(6) cells) from Brown-Norway (BN) rats into major histocompatibil ity complex (MHC) incompatible Lewis recipients largely failed to prolong k idney allograft viability from the same donor transplanted 60, 40, or 30 da ys after cell infusion. A short course of cyclosporine (per se. unable to p rolong graft survival) was started at the same day of donor leukocyte infus ion, but instead was able to prolong the survival of the BN kidney transpla nt-performed 40 days later-but not of a Wistar Furth (WF) third party, with some animals even developing tolerance. A mixed lymphocyte reaction of hos t cells from long-term surviving rats to BN stimulator cells was significan tly reduced as compared with controls. Donor BN DNA was detected in the per ipheral blood of Lewis rats until day 40 after BN leukocyte infusion. Micro chimerism persisted (60 to 70 days post-transplant) in most long-term graft recipients. Reducing the time interval between donor leukocyte infusion an d subsequent kidney transplant to 10 days still prolonged graft survival. D onor peripheral blood mononuclear cells, but not polymorphonuclear cells, i n the leukocyte preparation contributed to prolong kidney allograft surviva l. Conclusions. Pretransplant donor leukocyte infusion under the appropriate c onditions can tip the immune balance toward improved graft acceptance. This result could be relevant to the achievement of donor-specific tolerance of the graft with the maintenance of an intact response to third-party antige ns.