Facilitation of Skin Allograft Survival by Blood Leucocyte Extracts

Abstract

Fresh and frozen-stored mitochondrial, microsomal, and endoplasmic reticulum extracts of blood leucocytes act as potent alloantigens in human recipients. Similar results were obtained with freshly prepared extracts consisting of mixtures of all cytoplasmic fractions; storage of such mixtures at −20 C, followed by 1–2 hr thawing at 37 C abrogated their capacity to induce allograft sensitivity in 45 of 47 recipients. Donor-specific skin allografts and grafts from other sources exhibited significant attentuations in the tempo and intensity of rejection, ranging from first-set rejection to chronic rejection and/or to prolongations in allograft survival. In contrast with the 66.2% rejection rate of first-set skin grafts at 10 days in 71 normal subjects, only 29% of skin grafts from the leucocyte donor applied to 24 recipients of 0.1 to 9 Transplantation Antigen (T.A.) units of pooled cytoplasmic mixtures were rejected by that time. Only 17.4% similar grafts in 23 recipients of 25 to 515 T.A. units were rejected at 10 days. Seventeen skin grafts placed on recipients of 45 to 140 T.A. units of the same cytoplasmic preparation exhibited a slow rejection characterized by progressive shrinkage and eventual disappearance, with no evidence of hemorrhagic necrosis (chronic skin graft rejection). These results support the possibility that the attenuations in allograft reactivity observed in patients with end-stage renal disease after blood transfusions may be related to the leucocyte components of such transfusions. The capacity of blood transfusions to decrease reactivity to renal allografts in uremic patients maintained on hemodialysis stands in contrast with the ability of such transfusions to sensitize normal human recipients to donor-specific skin allografts. The differential effect may be related to the immunosuppressed state(s) documented in the uremic population, and/or the use of immunosuppressive drug therapy in such patients at the time of transplantation and thereafter.