Determining The Intrathymic Mechanisms That Instruct Regulatory T-cell Production For Control Of Organ Specific Autoimmunity (360G-Wellcome-203858_Z_16_A)

T-cells recognise and mount an immune response against pathogens however responses against self-tissue can occur, causing tissue damage and disease. In the thymus (a unique organ of T-cell development and education) autoreactive T-cells are removed but this isn’t 100% efficient, meaning a sub-population of T-cells termed regulatory T-cells (Tregs) is required to prevent self-reactivity. Our understanding of Treg development is incomplete and has been further challenged by findings of high heterogeneity in the thymic Treg population i.e. a large population of mature vs de novo Tregs. Furthermore possible Treg development outside the thymus by the most recent thymic emigrants (RTEs) remains unexplored. To accurately assess Treg development we use a novel mouse model with fluorescent markers that identify both a) Treg vs. non-Treg, and b) age. Distinguishing a cells identity along with its age allows us to investigate new and old Tregs in the thymus as well as Treg RTEs in the periphery using techniques such as flow cytometry, microscopy and qPCR to characterise thymic and extrathymic developmental stages. This work will provide new insight into how Tregs which regulate discreet tissue sites are generated, offering valuable new information on an essential regulator of self-reactivity and disease.