Migration of lymphocytes from blood vessels into pancreatic lymph nodes (PanLNs) and pancreas is critical for the development of islet inflammation and beta cell destruction in type 1 diabetes (T1D). Adhesion of lymphocytes to the luminal surface of blood vessel endothelia in PanLNs and pancreas is an important step in this migration. However, the adhesion molecules that control migration of lymphocytes into human PanLNs and pancreas during the development of T1D are not well defined.

The goals of our project are to determine which endothelia adhesion molecules, and their lymphocyte receptors, are highly expressed in human PanLNs and pancreas during development of T1D, as compared to pancreas and PanLNs of controls (Aims 1 and 2). The physiologic importance of adhesion molecules that are expressed on lymphocytes and endothelia of PanLNs and pancreas during development of T1D will be determined using Stamper-Woodruff in vitro binding assays (Aims 3 and 4). Successful completion of these studies will help define the immunological mechanisms that are important for the development of islet inflammation and beta cell destruction in human T1D.