Posttransplant administration of allochimeric major histocompatibility complex class-I molecules induces true transplantation tolerance

Abstract

Background. Allochimeric class-I major histocompatibility complex (MHC) molecules that contain donor-type immunogenic epitopes displayed on recipient-type sequences were shown to induce transplantation tolerance when administered at the time of transplantation. Here, we investigated the ability of posttransplant allochimeric administration to induce tolerance and concomitantly inhibit chronic rejection. Methods. Allochimeric (α1h1/u)-RT1.Aa class-I MHC antigenic extracts were administered by way of the portal vein into ACI recipients of Wistar-Firth (WF) hearts at days +3, +7, and +10 posttransplantation in conjunction with subtherapeutic oral cyclosporine. Results. Delayed posttransplant allochimeric administration induced donor-specific transplantation tolerance to rat cardiac allografts. In contrast, delayed delivery of unaltered donor- or recipient-type MHC extracts failed to prolong allograft survival. In addition, histopathologic examination or estimation of transplant vascular sclerosis by neointimal index assessment, following delayed allochimeric therapy, revealed intact global architecture and minimal intimal thickening, respectively. Conclusion. Allochimeric MHC class-I therapy is a unique and novel clinically applicable approach for induction of "true" transplantation tolerance where chronic rejection is concomitantly abrogated.