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BOR - Papers in Press, published online ahead of print January 19, 2005.
Biol Reprod 2005, 10.1095/biolreprod.104.038315
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BIOLOGY OF REPRODUCTION 72, 1224–1231 (2005)
DOI: 10.1095/biolreprod.104.038315
© 2005 by the Society for the Study of Reproduction, Inc.

Neonatal Porcine Sertoli Cells Inhibit Human Natural Antibody-Mediated Lysis1

Jannette M. Dufour 3,4 , Meredith Hamilton 3, Ray V. Rajotte 3,4,5  , and Gregory S. Korbutt 2 3,4,5  

Surgical-Medical Research Institute,3 Department of Surgery,4 Department of Medicine,5 University of Alberta, Edmonton, Alberta, Canada T6J 6J5

Sertoli cells protect cotransplanted cells from allogeneic and xenogeneic rejection. Additionally, neonatal porcine Sertoli cells (NPSCs) survive long-term as xenografts in nonimmunosuppressed rodents. This has led to the hypothesis that NPSCs could be used to prevent cellular rejection in clinical transplantation, thereby eliminating the need for chronic immunosuppression. Prior to transplantation of NPSCs in humans it is necessary to determine whether they are also protected from humoral-mediated xenograft rejection. The presence of Gal{alpha}(1,3)Galß(1,4)GlcNAc-R ({alpha}Gal epitope) as well as binding of human immunoglobulin G (IgG) and IgM to NPSCs was examined by immunocytochemical and fluorescence-activated cell sorter analysis. {alpha}Gal was detected on 88.5% ± 3.0% of NPSCs. Consistent with this, 71.7% ± 1.0% and 65.4% ± 5.2% of NPSCs were bound by IgG and IgM, respectively. When cultured NPSCs underwent an in vitro cytotoxicity assay by incubation with human AB serum plus complement, no increase in cellular lysis was observed, while controls—porcine aorta endothelial cells—were shown to contain >60% dead cells. Finally, activation of the complement cascade was examined by immunohistochemistry. C3 and C4 were deposited on the surface of the NPSC membrane, indicating activation of complement. Although the complement cascade was activated, the membrane attack complex (MAC) was not formed. These data demonstrate that despite expression of {alpha}Gal, binding of xenoreactive antibodies, and the activation of complement, NPSCs survive human antibody and complement-mediated lysis by preventing MAC formation. This suggests that NPSCs may be able to survive humoral-mediated rejection in a clinical situation.

immunology, male reproductive tract, Sertoli cells, testis

1 Supported in part by the Alberta Heritage Foundation for Medical Research (AHFMR), Canadian Institutes of Health Research (CIHR) grant FRN-8030, and the Juvenile Diabetes Research Foundation (JDRF). G.S.K. is a senior scholar of the AHFMR, and recipient of a Career Development Award from the JDRF. J.M.D. is a recipient of a Postdoctoral Fellowship from AHFMR and CIHR.

2 Correspondence: Gregory S. Korbutt, Surgical-Medical Research Institute, 1074 Dentistry/Pharmacy Centre, University of Alberta, Edmonton, Alberta, Canada T6G 2N8. FAX: 780 492 1627; korbutt{at}ualberta.ca






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Copyright © 2005 by the Society for the Study of Reproduction.