The application of xenotransplantation of porcine organs and tissues for treatment of disease, sought for more than a century, might soon be realized. Until now, the immune response of recipients against xenogeneic organs and tissues posed the main obstacle to clinical application. However, decades of research into this immune response and identification of other molecular barriers together with advances in genetic engineering and cloning of large animals and immune therapeutics coalesced to support prolonged survival and function of porcine organ grafts in nonhuman primates. This experimental progress in turn sparks consideration of clinical trials. The papers in this special section provide authoritative views concerning the immune hurdles that still limit and potentially still preclude clinical application of xenotransplantation. Xenoreactive antibodies elicited in T cell-dependent B cell-responses constitute the most important hurdle and control of these responses impels use of intense regimens of immunosuppression. These antibodies pose a danger to xenografts and potentially compromise subsequent allografts. However, new insights into the specificity of these antibodies, the pathways and kinetics of production and genetic determinants of pathogenicity offer novel opportunities for intervention. Likewise, the rapid ability to propose and test new strategies in nonhuman primate models hastens needed advances. However further progress will depend on development and validation of laboratory methods for identification and assay of pathogenic immune responses and evaluation of the response to therapy.
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