Support is requested for a Keystone Symposia meeting entitled Immunopathology of Type 1 Diabetes, organized by Drs. Kevan C. Herold, Dario A.A. Vignali, Jeffrey A. Bluestone and Anne Cooke. The meeting will be held in Whistler, British Columbia, Canada from April 4 - 9, 2013. The general topic of this meeting is relevant to the NIDDK mission with respect to Type 1 diabetes research and drug development. A great deal has been learned about the effectors and mechanisms of Type 1 diabetes from preclinical models and studies of samples from patients at risk and with the disease. However, despite this progress, translation of this understanding into new therapies that will have impact on patients has not been realized. The Keystone Symposia meeting on Immunopathology of Type 1 Diabetes will review our understanding of the mechanisms that are involved in the disease with consideration of the ways in which this understanding has resulted in clinical translation and how it has failed. Our goal is to integrate the most up to date understanding of mechanisms of autoimmune diabetes with studies in patients in order to identify ways in which developments in preclinical studies can provide insight into the past experiences in clinical studies and improve the design of future studies. The meeting will explore the following areas in detail: 1) What are the genetic determinants, immunopathology, and triggers of the disease? 2) What are the immune effectors that lead to beta cell destruction - how do they form and what are their functional characteristics? 3) How are immune effectors controlled in healthy individuals and how does this control fail in T1DM? 4) What has been the experience in restoring immune tolerance in humans - how can this be improved in the future? Opportunities for interdisciplinary interactions will be significantly enhanced by the concurrent meeting on Advances in the Knowledge and Treatment of Autoimmunity, which will share a keynote address and two plenary sessions with this meeting.