Impact of both donor and recipient strains on cardiac allograft survival after blockade of the CD40-CD154 costimulatory pathway

BACKGROUND: The effectiveness of anti-CD154 monoclonal antibodies in prolonging the survival of mouse allografts is dependent on the strain combination. In this report, we examined the impact of the donor and the recipient strains on the success of CD40-CD154 blockade. MATERIALS AND METHODS: Cardiac allograft survival was monitored in different donor/recipient strain combinations. Morphometric analyses on the allograft coronary arteries allowed quantification of vessel intimal thickening. RESULTS: Prolonged cardiac allograft survival after the administration of an anti-CD154 monoclonal antibody was found to be dependent on the donor and the recipient strains. The influence of the donor and the recipient strains lay in the ability of CD8 T cells to cause graft rejection despite CD40-CD154 blockade. Elimination of CD8 T cells before transplantation resulted in similar graft prolongation irrespective of the genotype of the donor or the recipient strain. CONCLUSION: These data show that both donor and recipient strains contribute to CD40-CD154-independent CD8 T-cell-mediated rejection.