Research being conducted by the Fife Laboratory:
Research in our lab is focused on understanding the fundamental mechanisms that regulate T lymphocytes during autoimmune disease such as Type 1 diabetes mellitus (T1DM). T1DM is an autoimmune disorder resulting from the T cell mediated destruction of the insulin producing cells within the pancreas. At the root of autoimmunity lies the most important aspect of immune regulation, the ability to discriminate between self and non-self. This highly selective response is characterized by a complicated set of mechanisms which regulate T lymphocyte activity. Autoimmunity results when these mechanisms fail. Recently, we have generated a powerful treatment protocol to selectively target autoreactive cells. Using this type of approach allows us to re-educate the immune system to selectively silence destructive immune responses. Thus in effect, restore a state of self-tolerance and prevent further tissue destruction. We have identified two key regulatory pathways that control diabetes and promote tolerance, Cytotoxic T lymphocyte antigen-4 (CTLA-4) and Programmed Death-1 (PD-1). We have shown that these pathways control both anergy induction and long term maintenance of tolerance. Recent studies have focused on the in vivo imaging of the immune response using two photon microscopy. Using this tolerance protocol will allow us to determine the precise roles of these negative regulatory pathways at different stages during disease pathogenesis to control immunity and enhance tolerance. The goal of our research is to better understand these processes to generate novel therapeutic targets to selectively silence self-destructive T cells.
