Current opinion in organ transplantation · 2009
Immune responses to alpha1,3 galactosyltransferase knockout pigs.
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Puga Yung Gisella, Schneider Mårten K J, Seebach Jörg D
Аннотация
PURPOSE OF REVIEW: To summarize the current knowledge of the immune response generated against xenografts stemming from alpha1,3-galactosyltransferase knockout (GalT-KO) pigs. In particular, we will address the nature of potentially remaining Gal epitopes, the role of non-Gal xenoantigens, and the cellular response directed against GalT-KO tissues.
RECENT FINDINGS: New findings support the view that porcine cells do not express isoglobotrihexosylceramide 3, and GalT-KO pigs, if at all, express negligible levels of Gal. The anti-non-Gal antibody response to GalT-KO cells allowed the identification of several potentially relevant porcine xenoantigens, mainly carbohydrates. Coculture of wildtype pig aortic endothelial cells but not of GalT-KO pig aortic endothelial cells with whole human blood induces the secretion of porcine and human cytokines and the upregulation of E-selectin; in contrast, the transmigration of human leukocytes across porcine endothelium is not regulated by Gal.
SUMMARY: New immunological problems are arising after the elimination of Gal by the generation of GalT-KO pigs; these include non-Gal antibodies and the identification of their elusive antigens, as well as cellular components of the immune system, including neutrophils, macrophages, natural killer cells, and T cells.
RECENT FINDINGS: New findings support the view that porcine cells do not express isoglobotrihexosylceramide 3, and GalT-KO pigs, if at all, express negligible levels of Gal. The anti-non-Gal antibody response to GalT-KO cells allowed the identification of several potentially relevant porcine xenoantigens, mainly carbohydrates. Coculture of wildtype pig aortic endothelial cells but not of GalT-KO pig aortic endothelial cells with whole human blood induces the secretion of porcine and human cytokines and the upregulation of E-selectin; in contrast, the transmigration of human leukocytes across porcine endothelium is not regulated by Gal.
SUMMARY: New immunological problems are arising after the elimination of Gal by the generation of GalT-KO pigs; these include non-Gal antibodies and the identification of their elusive antigens, as well as cellular components of the immune system, including neutrophils, macrophages, natural killer cells, and T cells.