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 (αDR) 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 αDR). The major site of DR expression in the islet was the endothelial cell surface. Endocrine cells were entirely of αDR binding. Nonislet endothelium was also heavily labeled, but acinar and ductal cells were completely negative. Leukocytes bound αDR 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.
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism