Accumulating evidence suggests that defective regulation is an essential underlying cause of autoimmunity. In the diabetes setting, the most prominent regulation is determined by the balance of pathogenic T cells and a small subset of CD4+ T lymphocytes known as regulatory T cells (Tregs) that are critical to maintaining peripheral self tolerance. This presentation will focus on attempts to alter this critical balance to re-instate immune tolerance in the autoimmune diabetes setting. Data will be presented in mouse models demonstrating the physiology of Treg development in the periphery including the identification of a novel dendritic cell subset that promotes Foxp3+ T cell differentiation. In addition, studies will be presented suggesting that PD-1 is a critical negative regulatory pathway in tolerance induction and maintenance. This work is supported by NIH grant R37 AI46643, JDRF Center Grant # 4-2004-372 and BD Biosciences.

Jeffrey A. Bluestone, Ph.D., holds the A.W. & Mary Margaret Clausen Distinguished Professorship in Metabolism and Endocrinology, a chair devoted to diabetes research at University of California, San Francisco. He is an immunobiologist recognized for his significant contributions towards elucidating the biological basis for immunologic tolerance. As one of the world's leading experts on why the body's immune system rejects or tolerates its own tissue, Bluestone has pioneered the development of new therapies to “re-tune” the immune response, reducing harmful autoimmune reactions as well as immune reactions against transplanted tissues and cells. He has helped to define the critical importance of T-cell co-stimulation in T-cell activation and has developed a humanized anti-CD3 monoclonal antibody that is currently in clinical trials for transplantation and autoimmune diseases. In addition, his pioneering research efforts have led to the development of CTLA-4Ig (Abatacept), a co-stimulation antagonist recently approved for the treatment of Rheumatoid Arthritis and potentially useful for a variety of other immune diseases. He maintains a basic research program and has a demonstrated commitment to the development of novel clinical applications.

Dr. Bluestone is currently the Director of the Diabetes Center at UCSF and Director of the Immune Tolerance Network, a consortium of more than 70 of the world's leading scientific researchers and clinical specialists from nearly 40 institutions with a mission to test new therapies designed to bring about immune tolerance in transplantation, autoimmune diseases, asthma and allergic diseases.

With over 300 publications to his credit, Dr. Bluestone has garnered numerous honors and awards including both the Mary Tyler Moore & Robert Levine Excellence in Clinical Research Award and the Gerold & Kayla Grodsky Distinguished Basic Scientist Award from the Juvenile Diabetes Research Foundation; American Cancer Society Faculty Scholar Award; the Cornel Medical School Distinguished Alumni Award; A Guggenheim Fellowship; A Fogarty Senior Research Fellowship; an NIH Merit Award; and election to the American Academy of Arts of Sciences.

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