Blockade of the CD28 and CD40 pathways result in the acceptance of pig andrat islet xenografts but not rat cardiac grafts in mice

Previously, we demonstrated that combination CTLA4-Fc and anti-CD40L mAb tr eatment results in tolerance to concordant, cellular islet xenografts. The aim of this study was to determine its effectiveness in a model of fetal pi g pancreas (FPP) xenotransplantation. Survival of FPP fragment grafts were compared to the survival of rat islet or cardiac xenografts following short term CTLA4-Fc and anti-CD40L mAb treatment. Rat islet and FPP fragment gra fts survived long-term. However, rat cardiac grafts were rejected by 52-91 days. Both rat islet and FPP grafts showed similar histology with intact is let structures and adjacent 'nests' of lymphocytes. Concordant vascularised rat hearts showed extensive polymorphonuclear infiltrate, concentric vascu litis and a perivascular infiltrate predominantly of CD8(+) T cells. This s uggests that this therapy is effective for prolonging islet xenografts and demonstrates that the cellular mechanism of rejection for vascularised and non-vascularised xenografts are different. (C) 2001 Elsevier Science B.V. A ll rights reserved.