The immune system is our body’s major defense mechanism against invading pathogens, as well as against tumor cells. One of the critical white blood cells that plays a central role in the immune system comprises T lymphocytes. They are generated from blood forming stem cells that undergo a series of discrete developmental stages within a specific organ called the thymus. This organ controls their proper development and this is mediated by another blood cell type, called dendritic cells, that may also develop in that same organ from the same precursors cells as the T cells. This, however, is still unclear and we wish to unravel this in this proposal. This is important because the interaction between both cell types is a critical element that prevents auto-immunity, such as type 1 diabetes. As such, our work will help to understand how defects in this process may occur and will also provide important novel insights into how T cells are generated in human. This will help us to restore T cell development in patients that suffer from T cell deficiencies, for instance as a result of genetic defects or due to chemo/radiotherapy for cancer treatment, or in settings of immune dysregulation such as auto-immunity. Since we study this in human and include functional analysis of patientderived mutations, our work has a strong translational impact on immune function, immune reconstitution and cancer treatment.