Elicited antibodies in baboons exposed to tissues from α1,3-galactosyltransferase gene-knockout pigs

Yau-Lin Tseng, Kathleen Moran, Frank J.M.F. Dor, Todd M. Sanderson, Wei Li, Courtney J. Lancos, Henk Jan Schuurman, David H. Sachs, David K.C. Cooper

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Abstract

Background. This study investigates anti-nonGal antibodies (Abs) in baboons after α1,3-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 haplotype. After adsorption of anti-Gal Abs, the elicited anti-nonGal Abs showed similar binding to PBMCs from pigs of all three haplotypes (SLAdd, SLAaa, SLAcc). 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.

Original languageEnglish
Pages (from-to)1058-1062
Number of pages5
JournalTransplantation
Volume81
Issue number7
DOIs
Publication statusPublished - 2006 Apr 1

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Galactosyltransferases
Gene Knockout Techniques
Papio
Swine
Anti-Idiotypic Antibodies
Antibodies
Haplotypes
Blood Cells
Flow Cytometry
Serum
Antigens
Antibody Specificity
Heart Transplantation
Immunosuppression
Adsorption
swine leukocyte antigen

All Science Journal Classification (ASJC) codes

  • Transplantation

Cite this

Tseng, Y-L., Moran, K., Dor, F. J. M. F., Sanderson, T. M., Li, W., Lancos, C. J., ... Cooper, D. K. C. (2006). Elicited antibodies in baboons exposed to tissues from α1,3-galactosyltransferase gene-knockout pigs. Transplantation, 81(7), 1058-1062. https://doi.org/10.1097/01.tp.0000197555.16093.98
Tseng, Yau-Lin ; Moran, Kathleen ; Dor, Frank J.M.F. ; Sanderson, Todd M. ; Li, Wei ; Lancos, Courtney J. ; Schuurman, Henk Jan ; Sachs, David H. ; Cooper, David K.C. / Elicited antibodies in baboons exposed to tissues from α1,3-galactosyltransferase gene-knockout pigs. In: Transplantation. 2006 ; Vol. 81, No. 7. pp. 1058-1062.
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title = "Elicited antibodies in baboons exposed to tissues from α1,3-galactosyltransferase gene-knockout pigs",
abstract = "Background. This study investigates anti-nonGal antibodies (Abs) in baboons after α1,3-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 haplotype. After adsorption of anti-Gal Abs, the elicited anti-nonGal Abs showed similar binding to PBMCs from pigs of all three haplotypes (SLAdd, SLAaa, SLAcc). 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.",
author = "Yau-Lin Tseng and Kathleen Moran and Dor, {Frank J.M.F.} and Sanderson, {Todd M.} and Wei Li and Lancos, {Courtney J.} and Schuurman, {Henk Jan} and Sachs, {David H.} and Cooper, {David K.C.}",
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Tseng, Y-L, Moran, K, Dor, FJMF, Sanderson, TM, Li, W, Lancos, CJ, Schuurman, HJ, Sachs, DH & Cooper, DKC 2006, 'Elicited antibodies in baboons exposed to tissues from α1,3-galactosyltransferase gene-knockout pigs', Transplantation, vol. 81, no. 7, pp. 1058-1062. https://doi.org/10.1097/01.tp.0000197555.16093.98

Elicited antibodies in baboons exposed to tissues from α1,3-galactosyltransferase gene-knockout pigs. / Tseng, Yau-Lin; Moran, Kathleen; Dor, Frank J.M.F.; Sanderson, Todd M.; Li, Wei; Lancos, Courtney J.; Schuurman, Henk Jan; Sachs, David H.; Cooper, David K.C.

In: Transplantation, Vol. 81, No. 7, 01.04.2006, p. 1058-1062.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Elicited antibodies in baboons exposed to tissues from α1,3-galactosyltransferase gene-knockout pigs

AU - Tseng, Yau-Lin

AU - Moran, Kathleen

AU - Dor, Frank J.M.F.

AU - Sanderson, Todd M.

AU - Li, Wei

AU - Lancos, Courtney J.

AU - Schuurman, Henk Jan

AU - Sachs, David H.

AU - Cooper, David K.C.

PY - 2006/4/1

Y1 - 2006/4/1

N2 - Background. This study investigates anti-nonGal antibodies (Abs) in baboons after α1,3-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 haplotype. After adsorption of anti-Gal Abs, the elicited anti-nonGal Abs showed similar binding to PBMCs from pigs of all three haplotypes (SLAdd, SLAaa, SLAcc). 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.

AB - Background. This study investigates anti-nonGal antibodies (Abs) in baboons after α1,3-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 haplotype. After adsorption of anti-Gal Abs, the elicited anti-nonGal Abs showed similar binding to PBMCs from pigs of all three haplotypes (SLAdd, SLAaa, SLAcc). 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.

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