Grant: Project Grant

Protection against pathogen infections and cancers is provided by the immune system. However, the immune system is responsible for the development of autoimmunity in genetically susceptible individuals. A white blood cell type critical for both immune protection and induction of autoimmunity is the T cell. During their development, T cells undergo rigorous selection processes in the thymus in an attempt to enrich the body with protective T cells and limit the presence of potentially harmful T cells. Much attention has been focused on the physical removal of T cells that recognize one's own healthy cells during development through a cell death mechanism. However, it is becoming clear that the ability of T cells to recognize one's own cells results in the generation of T cell populations that can protect against damage. Furthermore, we have evidence that, as opposed to the physical elimination of potentially harmful T cells, functional inactivation of these T cells is a more potent way to prevent autoimmunity. We propose to investigate the important events that regulate the development of protective T cell populations and to determine the relative importance of, and key molecules involved in, the functional inactivation of potentially harmful T cells during their development. Information generated from our experiments will provide valuable information into how the body normally avoids autoimmunity and will also generate insight into treatment options and therapeutics for cancer immunotherapy, chronic infections and organ transplantation.