Immune responses to alpha1,3 galactosyltransferase knockout pigs.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Puga Yung
Gisella
G
Service of Clinical Immunology and Allergology, Department of Internal Medicine, University Hospital and Medical Faculty, Geneva, Switzerland.
Schneider
Mårten K J
MK
Seebach
Jörg D
JD
D000818:Animals; D030801:Animals, Genetically Modified; D000906:Antibodies / Q000097:blood; D015478:Antigens, Heterophile / Q000276:immunology; D042783:Endothelial Cells / Q000276:immunology; D005700:Galactosyltransferases / Q000172:deficiency* / Q000235:genetics; D055786:Gene Knockout Techniques; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000235:genetics / Q000276:immunology*; D006801:Humans; D016377:Organ Transplantation; D013045:Species Specificity; D013552:Swine / Q000235:genetics* / Q000276:immunology; D023001:Transplantation Tolerance / Q000235:genetics; D014183:Transplantation, Heterologous; D014312:Trisaccharides / Q000276:immunology
D000906:Antibodies; D015478:Antigens, Heterophile; D014312:Trisaccharides; C076569:alpha-galactosyl epitope; D005700:Galactosyltransferases; C530267:alpha-1,3-galactosyltransferase 1, porcine