Grant: Operating Grant - Priority Announcement: Infection and Immunity (Bridge Funding)

The thymus is the principal organ for the generation of T cells, which play a key role in our defense against infectious diseases and cancer. However, alterations in T cell development can lead to the generation of pathogenic T cells that contribute to many autoimmune diseases, including diabetes, arthritis, and multiple sclerosis, or can result in the generation of leukemia. Once T-lymphocyte precursors enter the thymus from the bone marrow, their differentiation occurs in several discrete stages. We have defined early stages in thymocyte development, and also identified the key molecular interactions that are responsible for inducing T cell development. Our analyses revealed that these early thymocytes undergo a set regulated steps that leads them to commit to the T cell lineage. The goals of our studies are to determine the specific nature of signals that are provided by the thymic environment, and identify new molecules responsible for commitment, growth, and differentiation of lymphocyte precursors. These goals are aimed at developing an in vitro system that will support T cell differentiation, which would benefit numerous potential clinical applications towards the treatment of cancer, autoimmune disease, and AIDS.