Grant: Project Grant - Priority Announcement: Infection and Immunity

The immune system is instrumental in protecting individuals against infections and cancers, but can also cause autoimmune diseases in genetically susceptible individuals. A key cell type responsible for both protection and inducing autoimmunity is the T cell. To avoid causing autoimmunity, T cells undergo stringent selection process during their generation. There are many mechanisms that are used to prevent T cells from attacking healthy cells. We discovered that T cells can be rendered functionally incompetent during their development and that this method of preventing T cells from attacking healthy cells requires the PD-1 protein. This proposal seeks to determine the ways in which PD-1 functions to incapacitate T cells and whether other methods to prevent autoimmunity can control T cells that have not received a PD-1 signal. These studies will provide insight into how T cells are prevented from attacking healthy cells and provide opportunities to develop new treatments for individuals with autoimmunity. Additionally, given the clinical use of treatments that target PD-1 in people with cancer, we will learn more about how these therapies work and how they might trigger health complications.