ACCOMMODATION OF VASCULARIZED XENOGRAFTS - EXPRESSION OF PROTECTIVE GENES BY DONOR ENDOTHELIAL-CELLS IN A HOST TH2 CYTOKINE ENVIRONMENT

Organ xenografts under certain circumstances survive in the presence o f anti-graft antibodies and complement, a situation referred to as ''a ccommodation.'' We find that the endothelial cells (ECs) in hamster he arts that accommodate themselves in rats express genes, such as A20 an d bcl-2, that in vitro protect ECs from apoptosis and prevent upregula tion in those cells of proinflammatory genes such as cytokines, procoa gulant and adhesion molecules. Hearts that are rejected do not express these genes. In addition, vessels of rejected hearts show florid tran splant arteriosclerosis whereas those of accommodated hearts do not. A ccommodated xenografts have an ongoing T helper cell type 2 (Th2) cyto kine immune response, whereas the rejected grafts have a Th1 response. We propose a model for factors that contribute to the survival of xen ografts and the avoidance of transplant arteriosclerosis.