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Immune responses to alpha1,3 galactosyltransferase knockout pigs

Schneider, Marten K. J.
Published in Current opinion in organ transplantation. 2009, vol. 14, no. 2, p. 154-160
Abstract 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.
Keywords Animals*Animals, Genetically ModifiedAntibodies/bloodAntigens, Heterophile/immunologyEndothelial Cells/immunologyGalactosyltransferases/*deficiency/genetics*Gene Knockout TechniquesGraft Rejection/genetics/immunology/*prevention & controlGraft Survival/genetics/*immunologyHumans*Organ TransplantationSpecies SpecificitySwine/*genetics/immunologyTransplantation Tolerance/geneticsTransplantation, HeterologousTrisaccharides/immunology
PMID: 19300259
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Research group Laboratoire d'immunologie translationnelle (856)
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PUGA YUNG, Gisella, SCHNEIDER, Marten K. J., SEEBACH, Jorg Dieter. Immune responses to alpha1,3 galactosyltransferase knockout pigs. In: Current opinion in organ transplantation, 2009, vol. 14, n° 2, p. 154-160. doi: 10.1097/MOT.0b013e328329250d https://archive-ouverte.unige.ch/unige:20048

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Deposited on : 2012-04-23

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