title: Genetic engineering as an approach to xenotransplantation.
abstract: A discordant organ xenograft, such as a heart or kidney transplanted from pig to human, is rejected within 1 to 2 hours by a process called hyperacute rejection (HAR) caused in large or full measure by preexisting host xenoreactive natural antibodies (XNAs) and complement. HAR can be averted by blocking either complement or XNAs; but the xenograft is then rejected at 3 to 4 days by a process called delayed xenograft rejection (DXR), which can occur without the presence of T cells. DXR involves type II endothelial cell (EC) activation (the phase of activation that includes up-regulation of proinflammatory genes in the EC), infiltration into the graft of host monocytes and natural killer cells (both of which appear to be activated), and a complex cytokine picture. We discuss in this paper various approaches that might help prevent DXR, after which we assume that one would still have to deal with a xenograft counterpart of the T cell-mediated allograft rejection response. The approach to avoiding DXR focuses largely on genetic engineering of the ECs in the graft.
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: F H
authors.initials: FH
authors.lastname: Bach
mesh_terms: D000818:Animals; D000910:Antibodies, Heterophile / Q000235:genetics / Q000276:immunology; D003165:Complement System Proteins / Q000235:genetics / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D004730:Endothelium, Vascular / Q000276:immunology*; D005818:Genetic Engineering / Q000379:methods; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival; D006801:Humans; D016377:Organ Transplantation; D014183:Transplantation, Heterologous / Q000276:immunology; D015854:Up-Regulation / Q000235:genetics
chemical_list: D000910:Antibodies, Heterophile; D003165:Complement System Proteins