Anti-CD43 monoclonal antibody L11 flocks migration of T cells to inflamed pancreatic islets and prevents development of diabetes in nonobese diabeticmice

Nonobese diabetic mice are a well-known model for human insulin-dependent d iabetes mellitus. These mice develop autoimmune-mediated inflammation of th e pancreatic islets, followed by destruction of the insulin-producing beta cells and development of diabetes. Nonobese diabetic mice also have salivar y gland inflammation, and serve as a model for human Sjogren's syndrome. T cells are a prominent component of the inflammatory infiltrate in these sit es, and T cell recruitment from the blood is thought to be essential for th e initiation and maintenance of pathologic tissue damage. A unique mAb to m urine CD43, L11, has recently been shown to block the migration of T cells from blood into organized lymphoid tissues. Here we demonstrate that L11 si gnificantly inhibits T cell migration from blood into inflamed islets and s alivary glands, Treatment of nonobese diabetic mice with L11 from 1 to 4 or 8 to 12 wk of age led to significant protection against the development of diabetes. Moreover, protection was long-lived, with decreased incidence of diabetes even months after cessation of Ab administration. When treatment was started at 1 wk of age, L11 inhibited the development of inflammation i n pancreatic islets and salivary glands. L11 treatment had no long-term eff ect on numbers or phenotypes of peripheral lymphocytes, These data indicate that anti-CD43 Abs that block T cell migration may be useful agents for th e prevention or treatment of autoimmune diseases including insulin-dependen t diabetes mellitus and Sjogren's syndrome.