XENOTRANSPLANTATION

Transplantation of solid organs (heart, lung, liver, and kidney) from swine to humans would solve the current critical shortage of cadaver organs needed by patients with end-stage disease of these organs. In addition, transplantation between distant species (discordant xenografting) will require an understanding of a number of unique immunologic features. Discordant xenografts are rejected within minutes to hours after transplantation. This rejection is due to natural immunity by recipients never before exposed to the xenografts. In some species combinations, this fulminant rejection is due to naturally occurring pre-existing antibodies against the xenograft endothelium. In other species combinations, the xenograft activates the alternative pathway of complement. The swine to human species combination is the most clinically relevant. In this combination, natural human and private antibodies recognize alpha-galactosyl residues of glycoproteins and glycolipids. Potential future therapeutic measures to prevent natural immunity include the genetic engineering of human complement inhibitors into swine cell membranes or genetic ''knock out'' of the enzymes responsible for placing alpha-galactosyl residues on swine cell surfaces. There are also special considerations in acquired immunity against xenografts. Cytokines and adhesion molecules may not work across species lines. Xenograft antigens may have to be processed by host antigen-presenting cells in order to effectively stimulate the immune system.