Importance of the Gal alpha1-3 Gal antigen in discordant islet xenotransplantation: immunosuppression, which inhibits porcine islet xenograft rejection in ordinary mice, is equally effective in Gal-knockout mice.
BACKGROUND
Islet xenotransplantation will most likely be performed in diabetic patients treated with immunosuppressive drugs. The importance of the galactosyl alpha(1-3) galactose (Galalpha1-3Gal) 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 Galalpha1-3Gal. Evaluation was performed 12 days after transplantation using morphologic techniques. The levels of serum immunoglobulin (Ig)G and IgM to the Galalpha1-3Gal 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 Galalpha1-3Gal 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 Galalpha1-3Gal barrier.
Wennberg
L
L
Department of Transplantation Surgery, Karolinska Institute, Karolinska University Hospital, Huddinge, Sweden. lars.wennberg@hs.de
Song
Z
Z
Bennet
W
W
Sandberg
J O
JO
Sundberg
B
B
Thall
A
A
Korsgren
O
O
D000818:Animals; D000910:Antibodies, Heterophile / Q000097:blood; D015478:Antigens, Heterophile; D001323:Autoantibodies / Q000097:blood; D004187:Disaccharides / Q000276:immunology*; D005700:Galactosyltransferases / Q000172:deficiency / Q000235:genetics; D006084:Graft Rejection / Q000209:etiology / Q000276:immunology; D006801:Humans; D007114:Immunization; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008819:Mice, Nude; D034421:Sus scrofa; D014183:Transplantation, Heterologous
D000910:Antibodies, Heterophile; D015478:Antigens, Heterophile; D001323:Autoantibodies; D004187:Disaccharides; C024211:islet cell antibody; C055075:galactosyl-(1-3)galactose; D005700:Galactosyltransferases; C047006:N-acetyllactosaminide alpha-1,3-galactosyltransferase