IMPORTANCE OF THE GAL α1–3 GAL ANTIGEN IN DISCORDANT ISLET XENOTRANSPLANTATION: IMMUNOSUPPRESSION, WHICH INHIBITS PORCINE ISLET XENOGRAFT REJECTION IN ORDINARY MICE, IS EQUALLY EFFECTIVE IN GAL-KNOCKOUT MICE

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Abstract
Background. Islet xenotransplantation will most likely be performed in diabetic patients treated with immunosuppressive drugs. The importance of the galactosyl alpha(1–3) galactose (Galα1–3Gal) antigen in immunosuppressed islet xenograft recipients has not been studied. Methods. Fetal porcine islet-like cell clusters (ICCs) were transplanted into the renal subcapsular space of both Gal-knockout mice and ordinary mice. Transplantations were performed in untreated mice and mice immunosuppressed with cyclosporine A (CsA) plus 15-deoxyspergualin (DSG). Studies were also performed in immunosuppressed Gal-knockout mice that had been actively immunized against Galα1–3Gal. Evaluation was performed 12 days after transplantation using morphologic techniques. The levels of serum immunoglobulin (Ig)G and IgM to the Galα1–3Gal antigen or to the ICCs were determined. Results. No difference in the morphologic appearance could be seen between ordinary mice and Gal-knockout mice. No deposits of IgG, IgM, or C3 could be detected. Almost no difference could be seen between immunosuppressed Gal-knockout mice and immunosuppressed ordinary mice. In immunosuppressed, immunized Gal-knockout mice, the results were similar. In ordinary mice treated with CsA+DSG, the levels of anti-Gal IgM were lower than they were in untreated mice, whereas the levels of anti-Gal IgG were similar. In Gal-knockout mice (including immunized animals) treated with CsA+DSG, the levels of anti-Gal IgG and IgM were lower than they were in untreated Gal-knockout mice. Conclusions. After renal subcapsular transplantation, antibodies against Galα1–3Gal have no major influence on islet xenograft rejection in the pig-to-mouse model. Immunosuppression, which inhibits rejection in the pig-to-mouse model, is equally effective when transplantation is performed across the Galα1–3Gal barrier.

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