Elicited antibodies in baboons exposed to tissues from alpha1,3-galactosyltransferase gene-knockout pigs. 2006

Yau-Lin Tseng, and Kathleen Moran, and Frank J M F Dor, and Todd M Sanderson, and Wei Li, and Courtney J Lancos, and Henk-Jan Schuurman, and David H Sachs, and David K C Cooper
Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston, USA.

BACKGROUND This study investigates anti-nonGal antibodies (Abs) in baboons after alpha1,3-galactosyltransferase gene-knockout (GalT-KO) pig heart transplantation (Tx). METHODS Four baboons underwent pig heart Tx under chronic immunosuppression, which was discontinued after graftectomy. During follow-up, one baboon also received a pig splenocyte infusion. Hearts and splenocytes were from GalT-KO pigs (n = 3) or pigs with low Gal expression (Gal-low, n = 2), all of swine leukocyte antigen (SLA) dd haplotype. Several weeks after graftectomy, sera were tested by flow cytometry and cytotoxicity assay on porcine peripheral blood mononuclear cells (PBMC) for elicited anti-nonGal Abs. Sera were adsorbed on a Gal immunoaffinity matrix, and tested for SLA haplotype specificity using PBMC from SLA aa, cc, and dd haplotypes. RESULTS Before heart Tx, no baboon had anti-nonGal Abs demonstrable by binding or cytotoxicity to GalT-KO PBMC. All four baboons developed anti-nonGal Abs after Tx, demonstrable by flow cytometry, and three sera from baboons showed cytotoxicity to GalT-KO PBMC of SLA(dd) haplotype. After adsorption of anti-Gal Abs, the elicited anti-nonGal Abs showed similar binding to PBMCs from pigs of all three haplotypes (SLA(dd), SLA(aa), SLA(cc)). CONCLUSIONS Anti-nonGal Abs developed after GalT-KO pig heart Tx into baboons. The most potent of these antibodies appeared to detect antigens shared by the three pig haplotypes tested. It remains unclear whether these antibodies are directed towards shared SLA determinants or other pig antigens, and whether antibodies with specificity for allelic SLA determinants are also present, but at lower titer.

UI MeSH Term Description Entries
D007963 Leukocytes, Mononuclear Mature LYMPHOCYTES and MONOCYTES transported by the blood to the body's extravascular space. They are morphologically distinguishable from mature granulocytic leukocytes by their large, non-lobed nuclei and lack of coarse, heavily stained cytoplasmic granules. Mononuclear Leukocyte,Mononuclear Leukocytes,PBMC Peripheral Blood Mononuclear Cells,Peripheral Blood Human Mononuclear Cells,Peripheral Blood Mononuclear Cell,Peripheral Blood Mononuclear Cells,Leukocyte, Mononuclear
D010215 Papio A genus of the subfamily CERCOPITHECINAE, family CERCOPITHECIDAE, consisting of five named species: PAPIO URSINUS (chacma baboon), PAPIO CYNOCEPHALUS (yellow baboon), PAPIO PAPIO (western baboon), PAPIO ANUBIS (or olive baboon), and PAPIO HAMADRYAS (hamadryas baboon). Members of the Papio genus inhabit open woodland, savannahs, grassland, and rocky hill country. Some authors consider MANDRILLUS a subgenus of Papio. Baboons,Baboons, Savanna,Savanna Baboons,Baboon,Baboon, Savanna,Papios,Savanna Baboon
D003601 Cytotoxicity Tests, Immunologic The demonstration of the cytotoxic effect on a target cell of a lymphocyte, a mediator released by a sensitized lymphocyte, an antibody, or complement. AHG-CDC Tests,Anti-Human Globulin Complement-Dependent Cytotoxicity Tests,Microcytotoxicity Tests,Anti Human Globulin Complement Dependent Cytotoxicity Tests,Anti-Human Globulin Complement-Dependent Cytotoxicity Test,Antiglobulin-Augmented Lymphocytotoxicity Test,Antiglobulin-Augmented Lymphocytotoxicity Tests,Cytotoxicity Test, Immunologic,Cytotoxicity Tests, Anti-Human Globulin Complement-Dependent,Cytotoxicity Tests, Immunological,Immunologic Cytotoxicity Test,Immunologic Cytotoxicity Tests,Lymphocytotoxicity Test, Antiglobulin-Augmented,Lymphocytotoxicity Tests, Antiglobulin-Augmented,Microcytotoxicity Test,AHG CDC Tests,AHG-CDC Test,Anti Human Globulin Complement Dependent Cytotoxicity Test,Antiglobulin Augmented Lymphocytotoxicity Test,Antiglobulin Augmented Lymphocytotoxicity Tests,Cytotoxicity Test, Immunological,Cytotoxicity Tests, Anti Human Globulin Complement Dependent,Immunological Cytotoxicity Test,Immunological Cytotoxicity Tests,Lymphocytotoxicity Test, Antiglobulin Augmented,Lymphocytotoxicity Tests, Antiglobulin Augmented
D005690 Galactose An aldohexose that occurs naturally in the D-form in lactose, cerebrosides, gangliosides, and mucoproteins. Deficiency of galactosyl-1-phosphate uridyltransferase (GALACTOSE-1-PHOSPHATE URIDYL-TRANSFERASE DEFICIENCY DISEASE) causes an error in galactose metabolism called GALACTOSEMIA, resulting in elevations of galactose in the blood. D-Galactose,Galactopyranose,Galactopyranoside,D Galactose
D005700 Galactosyltransferases Enzymes that catalyze the transfer of galactose from a nucleoside diphosphate galactose to an acceptor molecule which is frequently another carbohydrate. EC 2.4.1.-. Galactosyltransferase
D006239 Haplotypes The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the MAJOR HISTOCOMPATIBILITY COMPLEX. Haplotype
D006649 Histocompatibility Antigens A group of antigens that includes both the major and minor histocompatibility antigens. The former are genetically determined by the major histocompatibility complex. They determine tissue type for transplantation and cause allograft rejections. The latter are systems of allelic alloantigens that can cause weak transplant rejection. Transplantation Antigens,Antigens, Transplantation,Histocompatibility Antigen,LD Antigens,SD Antigens,Antigen, Histocompatibility,Antigens, Histocompatibility,Antigens, LD,Antigens, SD
D000483 Alleles Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product. Allelomorphs,Allele,Allelomorph
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000910 Antibodies, Heterophile Antibodies elicited in a different species from which the antigen originated. These antibodies are directed against a wide variety of interspecies-specific antigens, the best known of which are Forssman, Hanganutziu-Deicher (H-D), and Paul-Bunnell (P-B). Incidence of antibodies to these antigens--i.e., the phenomenon of heterophile antibody response--is useful in the serodiagnosis, pathogenesis, and prognosis of infection and latent infectious states as well as in cancer classification. Antibodies, Heterogenetic,Antibodies, Heterotypic,Antibodies, Xenogeneic,H-D Antibodies,Hanganutziu-Deicher Antibodies,Heteroantibodies,Heterologous Antibodies,Heterophile Antibodies,P-B Antibodies,Paul-Bunnell Antibodies,Xenoantibodies,Antibodies, Heterologous,Antibodies, Heterophil,Antibodies, Xenogenic,Forssman Antibody,Heterogenetic Antibodies,Antibody, Forssman,Heterophil Antibodies,Heterotypic Antibodies,Xenogeneic Antibodies,Xenogenic Antibodies

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