Absence of host B7 expression is sufficient for long-term murine vascularized heart allograft survival

CD28 antagonists have been shown to promote longterm graft survival and ind uce donor-specific tolerance. In this study, the role of CD28/B7 costimulat ion and the relative importance of host versus donor B7 expression in allog raft rejection was assessed in a murine abdominal vascularized heterotopic heart transplant model. Wild-type, CD28-deficient, or B7-1/B7-2-deficient C 57BL/6 (B6) mice were grafted with allogeneic wild type or B7-1/B7-2-defici ent hearts. The results demonstrate allogeneic heart grafts survive long-te rm in mCTLA4Ig-treated B6 and untreated B7-1/B7-2-deficient B6 recipients b ut not CD28KO B6 mice. B7-1/B7-2KO Re recipients treated with anti-CD28 (PV -1) or recombinant human IL-2 rejected the heart transplants indicating tha t these mice are immunologically competent to reject grafts if costimulator y signals are supplied or bypassed. Finally, there was no difference in rej ection between normal animals transplanted with wild-type versus B7-1/B7-2- deficient hearts. These results support a critical role for B7-expressing h ost antigen presenting cells in the rejection of heart allografts in mice a nd differences among B7KO and CD28KO animals.