Research Abstracts Online
January 2009 - March 2010
University of Minnesota Twin Cities
PI: Daniel L. Mueller
Epigenetic Control of T Cell Autoimmunity
Effective control of systemic autoimmune diseases such as rheumatoid arthritis (RA) currently relies on the use of intense generalized immunosuppression, thus increasing the risk of infection and malignancy. A better theoretical approach to the treatment of autoimmune disease is the induction of an antigen-specific tolerance that targets only the dangerous self-reactive T and B cells. The design of such effective therapies with the potential to cure autoimmune disease, however, is hampered by our inability to visualize and study those self antigen-specific polyclonal lymphocytes within the intact immune system. Furthermore, we lack sufficient knowledge regarding the induction of clonal anergy in lymphocytes that are already responding to self-antigens within the diseased individual. Finally, the typical candidate approach to the identification of new therapeutic targets is an inherently slow process that can be adversely influenced by preconceived notions about the molecular mechanisms that are important to the induction of anergy.
These researchers are using emerging antigen/class II tetramer technologies to track polyclonal CD4+ T cells that break immune tolerance and cause autoimmunity. They have two main aims for this project: to investigate the individual roles of NT5’E and Foxp3 in the development and maintenance of clonal anergy following initial self antigen encounter by polyclonal CD4+ T cells in the peripheral immune system, and to establish the role of NT5’E in the epigenetic changes that protect against the development of CD4+ T cell-mediated arthritis.
Sara Nandiwada, Research Associate