Mixed hematopoietic chimerism prevents allograft vasculopathy.
BACKGROUND
Mixed hematopoietic chimerism has been shown to induce long-term acceptance of transplant organs. We determined whether mixed chimerism prevented allograft vasculopathy, using the rat aortic allograft model.


METHODS
Mixed chimeras were prepared by reconstituting lethally irradiated (1100 cGy) WF rats with a mixture of T-cell depleted (TCD) syngeneic (WF) plus TCD allogeneic (ACI) bone marrow. Donor-specific (ACI) or third-party (F344) aortic grafts were transplanted into mixed chimeric animals 1 to 2 months after bone marrow reconstitution. No immunosuppressive drugs were administered. At 30 days postoperatively, aortic allografts were harvested for histology and measurement of cytokine mRNA by semiquantitative RT-PCR. Some aortic grafts were harvested at 90 and 180 days after transplantation for histological analysis. The degree of intimal hyperplasia and cytokine gene expression were compared among 4 groups: I (syngeneic; ACI donors to ACI recipients), II (allografts; ACI to WF), III (donor specific; ACI donor to chimeras) and IV (third-party; F344 to chimeras).


RESULTS
There was no difference in the degree of intimal hyperplasia (IH) between groups I and III. Groups II and IV had significantly more IH than group I. Compared to group I, levels of mRNA for IFN-y, IL-2, IL-10 and iNOS in groups II and IV were higher, while there was no difference in mRNA levels between group I and III.


CONCLUSIONS
These data suggest that mixed chimerism prevents allograft vasculopathy. Mixed chimerism holds great promise in clinical transplantation as a means to prevent allograft vasculopathy.
Department of Surgery, University of Pittsburgh School of Medicine, Pennsylvania, USA.
N
N
Kawaharada
L L
LL
Shears
S
S
Li
S M
SM
Pham
D000818:Animals; D001011:Aorta / Q000473:pathology / Q000637:transplantation*; D016026:Bone Marrow Transplantation / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000235:genetics; D005352:Fibromuscular Dysplasia / Q000276:immunology* / Q000473:pathology; D005786:Gene Expression Regulation / Q000502:physiology; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D008212:Lymphocyte Depletion; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018183:Transplantation Chimera / Q000276:immunology*; D014184:Transplantation, Homologous
D016207:Cytokines; D012333:RNA, Messenger