Expression of Complement Regulatory Proteins in Accommodated Xenografts Induced by Anti‐α‐Gal IgG1 in a Rat‐to‐Mouse Model

Anti‐graft antibodies are often associated with graft rejection. Under special conditions, grafts continue to function normally even in the presence of anti‐graft antibodies and complement. This condition is termed accommodation. We developed a xenograft accommodation model in which baby Lewis rat hearts are transplanted into Rag/GT‐deficient mice, and accommodation is induced by repeated i.v. injections of low‐dose anti‐α‐Gal IgG1. The accommodated grafts survived a bolus dose of anti‐α‐Gal IgG1, while freshly transplanted second grafts were rejected. To study the mechanism of anti‐α‐Gal IgG1‐mediated accommodation, both real‐time PCR and immunohistochemical staining revealed elevated expression of DAF, Crry and CD59 in the accommodated grafts. In vitro exposure of rat endothelial cells to anti‐α‐Gal IgG1 also induced the up‐regulation of DAF, Crry and CD59, as revealed by Western blot analyses, and was associated with an acquired resistance to antibody and complement‐mediated lysis in vitro. Collectively, these studies suggest that the up‐regulation of complement regulatory proteins may abrogate complement‐mediated rejection and permit the development of xenograft accommodation.

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