Islet allo- and xenotransplantation in normal, intercellular adhesion molecule-1-deficient, and P selectin-deficient mice.

Abstract

Recently, inhibition of transplant rejection by pretreatment of xenogeneic pancreatic islets cells with antibodies to intercellular adhesion molecule (ICAM)-1 was reported. These promising results together with the development of mice deficient in P selectin or ICAM-1 encouraged further evaluation of the role of these two molecules in allo- and xenogeneic pancreatic islet transplantation. These deficient mice provide powerful tools to study the complex role of cell adhesion molecules in the cellular interactions between graft and recipient that culminate in graft rejection. ICAM-1-deficient mice served as both donors and recipients, but P selectin-deficient mice served only as recipients, in allogeneic and concordant xenogeneic (mouse-to-rat) transplantations. Both ICAM-1- and P selectin-deficient mice served as recipients in discordant xenogeneic (pig to mouse) transplantations. Two hundred collagenase-isolated pancreatic islets or fetal porcine islet-like cell clusters were transplanted under the renal capsule of the recipients. Animals were killed 7 days after transplantation, and the rejection process was evaluated with immunohistochemical techniques. The use of ICAM-1- or P selectin-deficient mice did not influence the infiltration of T cells, macrophages, or natural killer cells in the islet grafts. Nor did preincubation of islet-like cell clusters with ICAM-1 monoclonal antibody inhibit the xenogeneic rejection process. In allograft rejection, an equivalent number of T cells and macrophages were present. Among the T cells, the CD8-positive subtype dominated. Quite in contrast, macrophages were the dominating infiltrating cell type in the discordant xenografts. The pattern of cellular infiltration in the concordant xenografts was more complex and seemed to share components from both allo- and xenograft rejection. Thus, disturbance of the expression of ICAM-1 or P selectin in either the recipient or in the islet-graft did not influence allo- or xenograft rejection.