Elicited antibodies in baboons exposed to tissues from alpha1,3-galactosyltransferase gene-knockout pigs.
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.
Tseng
Yau-Lin
YL
Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston, USA.
Moran
Kathleen
K
Dor
Frank J M F
FJ
Sanderson
Todd M
TM
Li
Wei
W
Lancos
Courtney J
CJ
Schuurman
Henk-Jan
HJ
Sachs
David H
DH
Cooper
David K C
DK
D000483:Alleles; D000818:Animals; D030801:Animals, Genetically Modified; D000910:Antibodies, Heterophile / Q000097:blood* / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D005690:Galactose / Q000276:immunology*; D005700:Galactosyltransferases / Q000235:genetics*; D006239:Haplotypes; D016027:Heart Transplantation / Q000276:immunology*; D006649:Histocompatibility Antigens / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D010215:Papio; D013552:Swine; D013556:Swine, Miniature; D014183:Transplantation, Heterologous / Q000276:immunology*
D000910:Antibodies, Heterophile; D006649:Histocompatibility Antigens; D005700:Galactosyltransferases; C047006:N-acetyllactosaminide alpha-1,3-galactosyltransferase; D005690:Galactose