Grant: Project Grant

The immune system protects individuals against infections and cancers, but can also cause autoimmune diseases in some 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 different ways that are used to prevent T cells from attacking healthy cells. We discovered that T cells can be turned non-functional during their generation and that this method of preventing T cells from attacking healthy cells requires the PD-1 protein. This proposal seeks to understand the ways that PD-1 functions to inactivate 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 use of drugs that target PD-1 in people with cancer, we will learn more about how these drugs work and how they might trigger health complications.