Immunogenicity of Allograft Components III: Immunogenic Components in the Rat Heart Allografts and Reduction of Immunogenicity of Leukocytes by Pretreatment of the Cell Donor

Abstract

Enzymatically disaggregated DA hearts were fractionated into three components, one isolated for endothelial cells, another for myocardial cells and the third for passenger cells. Cells of each component were used separately to prime AgB-incompatible AO recipients in the “primed rejection assay”, PRA. The primed recipients were transplanted 72 hours later with a DA heart allograft. Only cells of the passenger-enriched component induced accelerated rejection, indicating that the most immunogenic component in rat heart is indeed, the passenger population. DA spleen cells were then used to simulate the passenger cells in an attempt to elucidate the mechanisms of survival prolongation by donor pretreatment. DA strain rats were pretreated with different cytotoxic drugs known to prolong strongly, moderately or not at all the survival of a heart allograft by donor pretreatment. Their spleen cells were harvested 6 hours later and used either (a) to prime AO recipients for the PRA or (b) as stimulator cells in one-way mixed lymphocyte culture. With one exception, the drugs capable of prolonging graft survival failed to induce accelerated rejection and were non-stimulating or only weakly stimulating in the MLC. The drug pretreatment did not significantly alter the survival of stimulator cells in vitro. In summary, the results are compatible with an earlier hypothesis that donor pretreatment primarily affects the passenger leukocyte component of the organ allograft by reducing its immunogenicity.