ISLET ALLOTRANSPLANTATION AND XENOTRANSPLANTATION IN NORMAL, INTERCELLULAR-ADHESION MOLECULE-1-DEFICIENT, AND P-SELECTIN-DEFICIENT MICE

Background. Recently, inhibition of transplant rejection by pretreatme nt of xenogeneic pancreatic islets cells with antibodies to intercellu lar adhesion molecule (ICAM)-1 was reported. These promising results t ogether with the development of mice deficient in P selectin or ICAM-1 encouraged further evaluation of the role of these two molecules in a llo-and xenogeneic pancreatic islet transplantation. These deficient m ice provide powerful tools to study the complex role of cell adhesion molecules in the cellular interactions between graft and recipient tha t culminate in graft rejection. Methods. ICAM-1-deficient mice served as both donors and recipients, but P selectin-deficient mice served on ly as recipients, in allogeneic and concordant xenogeneic (mouse-to-ra t) transplantations. Both ICAM-1- and P selectin-deficient mice served as recipients in discordant xenogeneic (pig to mouse) transplantation s. 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 techniqu es. Results. The use of ICAM-1- or P selectin-deficient mice did not i nfluence the infiltration of T cells, macrophages, or natural killer c ells in the islet grafts. Nor did preincubation of islet-like cell clu sters 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 CDS-positive subtype dominated. Quite in contrast, macrophages were the dominating infiltra ting cell type in the discordant xenografts. The pattern of cellular i nfiltration in the concordant xenografts was more complex and seemed t o share components from both allo-and xenograft rejection.