Incidence and cytotoxicity of antibodies in cynomolgus monkeys directed to nonGal antigens, and their relevance for experimental models.
The recent availability of pigs homozygous for alpha1,3-galactosyltransferase gene-knockout (GT-KO) has enabled the study of incidence and cytotoxicity of antibodies of cynomolgus monkeys directed to antigens other than Galalpha1,3Gal (Gal), termed nonGal antigens. To this aim, sera from 21 cynomolgus monkeys were tested by flow cytometry for binding of IgM and IgG to peripheral blood mononuclear cells (PBMC) from wild-type (WT) and GT-KO pigs. The sera were also tested for complement-dependent cytotoxicity to WT and GT-KO PBMC. Anti-WT IgM and IgG were found in 100% and 95%, respectively, and anti-GT-KO IgM and IgG in 76% and 66%, respectively, in the sera of the monkeys tested (P < 0.01). Whereas 100% of sera were cytotoxic to WT PBMC, only 76% were cytotoxic to GT-KO PBMC, and the level of cytotoxicity was significantly less (P < 0.01). Although the incidence and cytotoxicity of antibodies in monkey sera to GT-KO pig PBMC are significantly less than to WT PBMC, approximately three-quarters of the monkeys tested had cytotoxic antibodies to GT-KO PBMC. This incidence of cytotoxicity is significantly higher than that found in baboons and humans, suggesting the baboon may be an easier and possibly more suitable model to study antibody-mediated rejection of transplanted GT-KO pig organs and cells.
Rood
Pleunie P M
PP
The Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA 15261, USA.
Rood
Pleunic P M
PP
Hara
Hidetaka
H
Busch
Jamie L
JL
Ezzelarab
Mohamed
M
Zhu
Xiaocheng
X
Ball
Suyapa
S
Ayares
David
D
Awwad
Michel
M
Cooper
David K C
DK
D000818:Animals; D000910:Antibodies, Heterophile / Q000097:blood*; D003165:Complement System Proteins / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D000939:Epitopes; D005434:Flow Cytometry; D005700:Galactosyltransferases / Q000172:deficiency / Q000235:genetics; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000201:enzymology / Q000276:immunology; D008252:Macaca fascicularis / Q000276:immunology*; D013552:Swine; D014312:Trisaccharides / Q000276:immunology*
D000910:Antibodies, Heterophile; D000939:Epitopes; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D014312:Trisaccharides; C076569:alpha-galactosyl epitope; D003165:Complement System Proteins; D005700:Galactosyltransferases