XENOTRANSPLANTATION

Transplantation of solid organs (heart, lung, liver, and kidney) from swine to humans would solve the current critical shortage of cadaver o rgans needed by patients with end-stage disease of these organs. In ad dition, transplantation between distant species (discordant xenografti ng) will require an understanding of a number of unique immunologic fe atures. Discordant xenografts are rejected within minutes to hours aft er transplantation. This rejection is due to natural immunity by recip ients never before exposed to the xenografts. In some species combinat ions, this fulminant rejection is due to naturally occurring pre-exist ing antibodies against the xenograft endothelium. In other species com binations, the xenograft activates the alternative pathway of compleme nt. The swine to human species combination is the most clinically rele vant. In this combination, natural human and private antibodies recogn ize alpha-galactosyl residues of glycoproteins and glycolipids. Potent ial future therapeutic measures to prevent natural immunity include th e genetic engineering of human complement inhibitors into swine cell m embranes or genetic ''knock out'' of the enzymes responsible for placi ng alpha-galactosyl residues on swine cell surfaces. There are also sp ecial considerations in acquired immunity against xenografts. Cytokine s 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.