Treatment with total lymphoid irradiation, cyclosporin A and a monoclonal anti-T-cell antibody in a hamster-to-rat heart transplantation model: graft survival and morphological analysis.
Treatment with preoperative total lymphoid irradiation and post-transplant cyclosporin A has been shown to have a synergistic effect on graft survival in allo- and xenotransplantation. Specific monoclonal antibodies against T cells and T cell subpopulations could offer new ways of preventing graft rejection in xenotransplantation. Graft survival and histology were examined after total lymphoid irradiation plus cyclosporin A treatment versus cyclosporin A plus a monoclonal antibody in a concordant, heterotopic, hamster-to-rat heart transplantation model. Preoperative total lymphoid irradiation was given at a dose of 1.25 Gy, 12 times over a period of 3 weeks. Cyclosporin A at a dose of 12.5 mg/kg per day was administered perorally and OX-19, a pan T cell monoclonal antibody, was given as intraperitoneal injections at doses of 100 micrograms or 500 micrograms/kg per day from day 0 until graft rejection. While total lymphoid irradiation alone prolonged graft survival to 9.4 days, total lymphoid irradiation plus cyclosporin A extended graft survival to a mean of 22 days. Cyclosporin alone or combined with the monoclonal antibody could not increase graft survival significantly when compared to untreated animals, which rejected their grafts within 3.7 days. Vascular rejection was the characteristic morphological finding, even after some weeks of excellent graft function. In conclusion, total lymphoid irradiation and cyclosporin A had a synergistic effect on graft survival in this concordant xenotransplantation model, although recent impressive results from other groups could not be reproduced. Total lymphoid irradiation combined with cyclosporin A appears to delay a primary humoral graft rejection, while the mechanism of rejection, judged by histology, stays the same.
Steinbrüchel
D A
DA
Laboratory of Nephropathology, Odense University Hospital, Denmark.
Madsen
H H
HH
Nielsen
B
B
Larsen
S
S
Koch
C
C
Jensenius
J C
JC
Hougesen
C
C
Kemp
E
E
D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D006224:Cricetinae; D003524:Cyclosporins / Q000008:administration & dosage*; D006085:Graft Survival / Q000187:drug effects* / Q000276:immunology / Q000528:radiation effects; D016027:Heart Transplantation / Q000276:immunology* / Q000473:pathology; D007165:Immunosuppression Therapy; D008221:Lymphoid Tissue / Q000528:radiation effects*; D008297:Male; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D003524:Cyclosporins