Immunocytochemical localization of HLA-DR in human islets of Langerhans.

Previous reports of allogeneic transplantation studies in rodents have postulated that the primary carriers of Ia antigen in islets of Langerhans are passenger leukocytes. We sought to demonstrate directly the localization of the analogous human antigen, HLA-DR, in islet-enriched fractions (IEFs), utilizing a nonpolymorphic monoclonal anti-DR (alpha DR) antibody. The presence of DR in the IEFs was first demonstrated by radioimmunobinding assay. Light microscopic immunocytochemistry, in frozen sections of intact (unfixed) human pancreas, revealed a staining pattern suggestive of a vascular distribution of DR in islets. Ultrastructural localization of DR was then carried out by indirect immunoperoxidase labeling in the presence of NaN3 (to prevent internalization of bound alpha DR). The major site of DR expression in the islet was the endothelial cell surface. Endocrine cells were entirely devoid of alpha DR binding. Nonislet endothelium was also heavily labeled, but acinar and ductal cells were completely negative. Leukocytes bound alpha DR but were relatively rare in the IEFs. Human islets, therefore, clearly express HLA-DR, but predominantly on insular endothelial cells. Isolation of pure endocrine cell populations, specifically free of endothelium, would appear to be a rational approach to reducing immunogenicity in allogeneic transplantation.