THE ROLE OF CELL-ADHESION MOLECULES IN THE DEVELOPMENT OF IDDM - IMPLICATIONS FOR PATHOGENESIS AND THERAPY

IDDM is a chronic inflammatory disease in which there is autoimmune-me diated organ-specific destruction of the insulin-producing beta-cells in the pancreatic islets of Langerhans, The migration of autoreactive lymphocytes and other leukocytes from the bloodstream into the target organ is of clear importance in the etiology of many organ-specific au toimmune/inflammatory disorders, including IDDM, In IDDM, this migrati on results in lymphocytic invasion of the islets (formation of insulit is) and subsequent destruction of beta-cells Migration of lymphocytes from the bloodstream into tissues is a complex process involving seque ntial adhesion and activation events, This migration is controlled in part by selective expression and functional regulation of cell adhesio n molecules (CAMs) on the surface of lymphocytes and vascular endothel ial cells or in the extracellular matrix. Understanding the mechanisms that regulate lymphocyte migration to the pancreatic islets will lead to further understanding of the pathogenesis of IDDM, In this article , we summarize the recent advances regarding the function of CAMs in t he development of IDDM in animal models and in humans and discuss the potential for developing CAM-based therapies for IDDM.