Further evidence that NK cells may contribute to the development of cardiac allograft vasculopathy.

In prior experiments, we found that recipients, even though specifically tolerant of donor antigens, will develop striking cardiac allograft vasculopathy (CAV) in allogeneic mouse heart transplants. This suggested that innate immune responses, in addition to conventional adaptive immunity, may be involved in the development of CAV. We accordingly performed transplants in the parental-to-F1 combination seeking supportive evidence of NK cell activity directed against the vessels of parental donor transplants as a manifestation of "hybrid resistance." When such lesions were indeed found, we investigated their pathogenesis employing immunopathological analysis, in vitro measurements of NK cytotoxicity, and donor-specific T-cell activity in F1 recipients of parental donor hearts. We present evidence that NK cells can promote cardiac allograft vasculopathy. Since NK cell activity is not well targeted by current immunosuppressive therapy, its control may offer a valuable new possibility for improving the long-term outcome of transplanted organs.