Pre-transplant blood transfusion and cyclosporin A induce long-term hamster cardiac xenograft survival in immunocompetent rats.
BACKGROUND
In previous studies we have shown that pre-transplant hamster blood transfusion (HBT) can induce non-responsiveness in the T cell independent immunecompartment and result in tolerance towards hamster cardiac xenografts (Xgs) in T cell deficient athymic nude rats. In this study we test the combination of pre-transplant HBT with cyclosporin A (CSA) in immunocompetent Lewis rats.


METHODS
Before transplantation of a hamster cardiac Xg, 1 ml hamster blood was administered to nude rats or Lewis rats. CSA dissolved in olive oil was given orally at varying doses. Anti-hamster antibodies were measured by flowcytometry.


RESULTS
In nude rats HBT 3 days before transplantation resulted in 100% long-term survival >100 days (n=9). In Lewis rats, HBT resulted in hyperacute rejection (HAR) (n=6). Treatment of nude rats with CSA at doses varying from five to 20 mg/kg/day and treatment of Lewis rats with CSA five or 10 mg/kg/day did not effect Xg survival. However, treatment of Lewis rats with CSA 20 mg/kg/day led to long-term survival of five of nine Xgs (p <0.01). Combination of HBT with CSA 10 mg/kg/day in Lewis rats resulted in long-term survival of four of seven Xgs. HBT and CSA 20 mg/kg/day resulted in 100% long-term survival (n=9). Immunoglobulin M (IgM) increased after HBT and CSA in these Lewis rats, but decreased after transplantation and remained low over time. When CSA was discontinued, IgM increased and Xgs were rejected (n=3).


CONCLUSIONS
This study confirms that pre-transplant HBT results in long-term survival of hamster cardiac Xgs in nude rats. HBT and CSA have strong synergistic effects in immunocompetent Lewis rats. Combination of HBT with CSA treatment leads to long-term Xg survival in Lewis rats, whereas HBT alone results in HAR. The presence of T cells has a dominant influence on Xg survival after pre-transplant blood transfusion.
Vriens
Patrick W
PW
Department of Cardiothoracic Surgery, Stanford University Medical Center, Stanford, CA, USA.
Stoot
Jan H
JH
van der Steenhoven
Tim J
TJ
Hoyt
Grant
G
Bouwman
Eelco
E
Robbins
Robert C
RC
D000818:Animals; D000910:Antibodies, Heterophile / Q000097:blood; D001803:Blood Transfusion; D006224:Cricetinae; D016572:Cyclosporine / Q000494:pharmacology*; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology; D006085:Graft Survival; D016027:Heart Transplantation / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D051379:Mice; D011300:Preoperative Care; D051381:Rats; D011917:Rats, Inbred Lew; D011923:Rats, Nude; D013047:Specific Pathogen-Free Organisms; D014183:Transplantation, Heterologous / Q000276:immunology
D000910:Antibodies, Heterophile; D007166:Immunosuppressive Agents; D016572:Cyclosporine