Xenograft accommodation is accompanied by intragraft Th2 cytokines and vascular expression of protective genes

Abstract: We have studied the accommodation (survival of an organ graft in the presence 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. This 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: A20, Bcl-x_L, Bcl-2, and hemoxygenase, which we define as genes that prevent endothelial cells from undergoing responses that might lead to graft rejection. Surviving xenografts were also associated with intragraft Th2 cytokine expression. Rejected grafts did not express the protective genes and had a Thl pattern of cytokine expression. These studies indicate a potential mechanism linking molecular and cellular responses to development of xenograft accommodation.