XENOGRAFT ACCOMMODATION IS ACCOMPANIED BY INTRAGRAFT TH2 CYTOKINES AND VASCULAR EXPRESSION OF PROTECTIVE GENES

We have studied the accommodation (survival of an organ graft in the p resence of anti-graft antibodies and complement) of heterotopic Golden Syrian hamster heart xenografts transplanted to Lewis rat recipients. The rats were treated with cyclosporine A (15 mg/kg/day i.m.) for the duration of the experiment and for 11 days with cobra venom factor. T his regimen resulted in long-term xenograft survival in approximately 75% of cases. Analysis of endothelial cells (and smooth muscle cells) in long-surviving grafts showed expression of ''protective'' genes: A2 0, Bcl-x(L), Bcl-2, and hemoxygenase, which we define as genes that pr event endothelial cells from undergoing responses that might lead to g raft rejection. Surviving xenografts were also associated with intragr aft Th2 cytokine expression. Rejected grafts did not express the prote ctive genes and had a Th1 pattern of cytokine expression. These studie s indicate a potential mechanism linking molecular and cellular respon ses to development of xenograft accommodation.