Inhibition of natural killer cells results in acceptance of cardiac allografts in CD28(-/-) mice

Successful transplantation of allogeneic organs is an important objective i n modern medicine. However, sophisticated immune defense mechanisms, primar ily evolved to combat infections, often work against medical transplantatio n. To investigate the roles of natural and adaptive immune responses in tra nsplant rejection, we functionally inactivated key effector systems of the innate (NK cells) and the adaptive immune system (CD28-mediated costimulati on of T cells) in mice. Neither of these interventions alone led to accepta nce of allogeneic vascularized cardiac grafts. In contrast, inhibition of N K-receptor-bearing cells combined with CD28-costimulation blockade establis hed long-term graft acceptance. These results indicate a concerted interpla y between innate and adaptive immune surveillance for graft rejection. Thus we suggest that inactivation of NK-receptor-bearing cells could be a new s trategy for successful survival of solid-organ transplants.