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. CONCLUSION: 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.