Donor passenger leukocytes. Since the description of the passenger leukocyte theory of direct allo-reactivity, attempts have been made to deplete donor organs of passenger leukocytes either before or after transplantation, in order to prolong survival in allogeneic recipients. Irradiation of donors prior to transplantation is one method of removing passenger leukocytes and has proved successful in prolonging survival of grafts in animal models of transplantation (60, 61); however, this is not a feasible strategy for clinical transplantation. Passenger leukocytes can also be removed by ex vivo perfusion of the organ before transplantation, and this has shown some efficacy in animal models (62). Pharmacological depletion of DPL has been studied, and efficacy has been shown in animal transplantation models with the use of anti-MHC class II antibodies (63, 64); however, there were issues with specificity and whether or not the target cells were depleted. In addition, a study by Xxxxxxxx et al. reported the use of anti-CD45 antibodies in human renal transplantation, which were perfused into donor kidneys before transplantation, and showed efficacy in diminishing rejection episodes for patients (65). Recent work from our laboratory has demonstrated the effectiveness of a donor MHC class II-specific immunotoxin in a mouse kidney transplantation model, where donor cells were specifically killed and grafts survived indefinitely with normal function, reduced donor-specific antibody formation, and delayed rejection of third party skin grafts (66). This provides evidence for the efficacy of therapies aimed at the immune system of the donor rather than the recipient, and could be an approach to limit the use of systemic immunosuppression in the clinic.
