Long-term acceptance of rat cardiac allografts on the basis of adenovirus mediated CD40Ig plus CTLA4Ig gene therapies.

Background: We have previously demonstrated that blockade of either CD80/86-CD28 or CD40-CD154 costimulatory pathways by using adenovirus vector coding CTLA4Ig (AdCTLA4Ig) or CD40Ig (AdCD40Ig) genes induced donor-specific tolerance in rat liver transplantation. In this study, we asked whether these gene-therapy-based costimulation blockade would induce tolerance in cardiac transplantation.

Methods: Heterotopic heart transplantation was performed in a full major histocompatibility complex (MHC) barrier combination of ACI (RT1avl) to Lewis (LEW, RT1l) rats.

Induction of donor-specific tolerance by adenovirus-mediated CD40Ig gene therapy in rat liver transplantation.

Background: Blockade of CD40-CD40 ligand (CD154) costimulatory pathway with anti-CD154 antibody (Ab) prolongs allograft survival in experimental organ transplantations; however, repeated agent administration is needed to provide an adequate immunosuppression. Seeking for simple and effective approach to interfere this signaling, we applied adenovirus-mediated gene therapy by encoding CD40Ig gene (AdCD40Ig).

Methods: Liver graft from ACI (RT1av1) rat was transplanted orthotopically into LEW (RT1l) rat, and AdCD40Ig was given to animals via the penile vein immediately after grafting (n=6).