Rejection of Cardiac Xenografts Transplanted from α1,3-Galactosyltransferase Gene-Knockout (GalT-KO) Pigs to Baboons

https://doi.org/10.1111/j.1600-6143.2008.02444.xGet rights and content
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The use of α1,3-galactosyltransferase gene-knockout (GalT-KO) swine donors in discordant xenotransplantation has extended the survival of cardiac xenografts in baboons following transplantation. Eight baboons received heterotopic cardiac xenografts from GalT-KO swine and were treated with a chronic immunosuppressive regimen. The pathologic features of acute humoral xenograft rejection (AHXR), acute cellular xenograft rejection (ACXR) and chronic rejection were assessed in the grafts. No hyperacute rejection developed and one graft survived up to 6 months after transplantation. However, all GalT-KO heart grafts underwent graft failure with AHXR, ACXR and/or chronic rejection. AHXR was characterized by interstitial hemorrhage and multiple thrombi in vessels of various sizes. ACXR was characterized by TUNEL+ graft cell injury with the infiltration of T cells (including CD3 and TIA-1+ cytotoxic T cells), CD4+ cells, CD8+ cells, macrophages and a small number of B and NK cells. Chronic xenograft vasculopathy, a manifestation of chronic rejection, was characterized by arterial intimal thickening with TUNEL+ dead cells, antibody and complement deposition, and/or cytotoxic T-cell infiltration. In conclusion, despite the absence of the Gal epitope, acute and chronic antibody and cell-mediated rejection developed in grafts, maintained by chronic immunosupression, presumably due to de novo responses to non-Gal antigens.

In α 1,3-galactosyltransferase gene-knockout swine cardiac xenografts transplanted into baboons, this study showed prevention of hyperacute rejection and prolonged graft survival up to almost 6 months. However, rejection was not controlled by chronic immunosuppressive protocols, and acute and chronic antibody- and cellular-mediated rejection developed in the cardiac xenografts.

Key words:

Acute rejection
baboon
cellular rejection
chronic rejection
humoral rejection
xenotransplantation

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