Identification of Ia-bearing cells in rat, dog, pig, and human islets of Langerhans.

Abstract

Cells expressing Ia-like antigens (Ia) are believed to provide the primary recognition signals for allograft rejection. In order to clarify the localization of Ia within islets of Langerhans in animals most commonly used as transplantation models and in humans, we performed both light microscopic (LM) and electron microscopic (EM) immunocytochemical studies with the following panel of monoclonal antibodies directed against Ia: B1F6 (antidog, antirat, and antihuman Ia) and B2E8 (antidog and antihuman Ia), generated in our laboratory; OX6 (antirat Ia); and L243 (antihuman Ia). By LM, B1F6-labeled or B2E8-labeled dog islets and B1F6-labeled or OX6-labeled rat islets all exhibited Ia-specific localization on 0-15 spheroidal or stellate cells per islet. Ultrastructural identification of these cells by indirect immunoperoxidase labeling of unfixed isolated islets revealed Ia-specific cell surface binding mostly on sparsely distributed cells that exhibited ultrastructural characteristics typical of monocytes or macrophages; no specific correlation between cell shape and cell type was apparent by EM. The presence of a resident population of monocytes and macrophages in these islets was confirmed by cytochemical localization of nonspecific esterase activity. Islet endothelium was Ia-negative, as were endocrine cells. Studies of human islets with B1F6, B2E8, and L243 confirmed our preliminary findings that, although there exists a sparse population of Ia-positive leukocytes similar to those present in dog and rat islets, Ia is also expressed extensively and constitutively on the human islet vascular endothelium. This differential localization of Ia in rats and dogs compared with humans could have important implications for the development of successful strategies for the immunomodulation of human islet allografts. We have now shown by immunopurification of 125I-labeled splenocyte plasma membrane antigens, that our MoAbs B1F6 and B2E8 also recognize porcine Ia, and immunocytochemical studies with these MoAbs demonstrated that Ia is also localized on the vascular endothelium in pig islets. Hence, this species may prove to be uniquely suitable as a model in which the immune response functions of Ia-bearing islet endothelium can be explored.