en
Scientific article
English

Immune responses to alpha1,3 galactosyltransferase knockout pigs

Published inCurrent opinion in organ transplantation, vol. 14, no. 2, p. 154-160
Publication date2009
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 Modified
  • Antibodies/blood
  • Antigens, Heterophile/immunology
  • Endothelial Cells/immunology
  • Galactosyltransferases/*deficiency/genetics
  • *Gene Knockout Techniques
  • Graft Rejection/genetics/immunology/*prevention & control
  • Graft Survival/genetics/*immunology
  • Humans
  • *Organ Transplantation
  • Species Specificity
  • Swine/*genetics/immunology
  • Transplantation Tolerance/genetics
  • Transplantation, Heterologous
  • Trisaccharides/immunology
Citation (ISO format)
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
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ISSN of the journal1087-2418
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