Posttransplant administration of allochimeric major histocompatibility complex class-I-molecules induces true transplantation tolerance.
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 (alpha1h(1/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.


CONCLUSIONS
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.
Semiltova
Natalya
N
The Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California 90095-7054, USA.
Shen
Xiu-Da
XD
Fishbein
Michael C
MC
Gao
Feng
F
Slomowitz
Samuel J
SJ
Jiao
Qingsheng
Q
Mukherjee
Kaushik
K
Busuttil
Ronald W
RW
Kupiec-Weglinski
Jerzy W
JW
Ghobrial
Rafik M
RM
D000818:Animals; D001161:Arteriosclerosis / Q000276:immunology / Q000473:pathology; D002908:Chronic Disease; D006084:Graft Rejection / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000494:pharmacology*; D007108:Immune Tolerance / Q000187:drug effects*; D011183:Postoperative Complications / Q000188:drug therapy / Q000276:immunology; D051381:Rats; D011912:Rats, Inbred ACI; D011920:Rats, Inbred WF; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D017539:Tunica Intima / Q000276:immunology / Q000473:pathology
D015395:Histocompatibility Antigens Class I; D011993:Recombinant Fusion Proteins