Presentation of donor major histocompatibility complex class II antigens by dna vaccination prolongs heart allograft survival.
BACKGROUND
Donor major histocompatibility complex (MHC) antigens play an important role in both allograft rejection and tolerance. With the use of several animal models, it has been shown that presentation of donor antigens before transplantation can lead to allograft tolerance. Vaccination of animals with a DNA plasmid encoding an antigen enables highly efficient expression of the protein in vivo.


METHODS
In this study, we used DNA vaccination delivered through intramuscular, intraperitoneal, or intravenous routes to indirectly present donor antigens and to determine the effect in the modulation of the allograft response. LEW.1A recipients of a LEW.1W heart allograft were treated before grafting by vaccination with a plasmid encoding the donor RT1.D MHC class II or RT1.A class I molecules.


RESULTS
Only anti-MHC II vaccination significantly prolonged allograft survival compared with untreated rats. We observed a significant prolongation of heart allograft survival with the intramuscular route of injection, but surprisingly we found the intravenous and intraperitoneal routes to be the best.


CONCLUSIONS
After transplantation the anti-donor cellular response was significantly decreased in vaccinated rats. This was accompanied by a significant reduction in interferon-gamma mRNA expression in the grafted hearts and T helper 1-type alloantibody production, indicating that the vaccination modifies the alloresponse against the grafts.
Pêche
Hélène
H
Institut National de la Santé et de la Recherche Médicale Unit 437 and Institut de Transplantation et de Recherche en Transplantation, Nantes, France.
van Denderen
Bryce
B
Roussel
Jean Christian
JC
Trinité
Benjamin
B
Soulillou
Jean Paul
JP
Cuturi
Maria Cristina
MC
D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D007111:Immunity, Cellular / Q000276:immunology; D008297:Male; D010957:Plasmids; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014184:Transplantation, Homologous; D019444:Vaccines, DNA / Q000276:immunology* / Q000494:pharmacology*
D000949:Histocompatibility Antigens Class II; D012333:RNA, Messenger; D019444:Vaccines, DNA