Wellcome Trust Clinical PhD Programme at the University of Oxford: Determining the role of Foxp3 regulatory T-cells in vivo. (360G-Wellcome-087331_Z_08_Z)

Current understanding of the immune system has been radically influenced by the discovery of regulatory T-cells. No longer are aggressive and destructive immune cells thought to be the only players. There is more of an emphasis on the immune cells involved in policing immune responses and creating a state of tolerance to self antigens, so preventing autoimmunity. Regulatory T-cells (T-Reg cells) are a T-ceIl subset crucial to the initiation and maintenance of tolerance. These cells act in the periphery as a further immunological barrier to self reactive Tcells which have escaped central thymic deletion and could result in autoimmunity. The development of in vitro, let alone in vivo, assays has been hampered by the inability to accurately identify T-Reg cells by cell surface markers alone. Previously, cells would have to be pernieabilised to look for foxP3 gene expression, a recently discovered intracellular marker of TReg cell generation. Such cells could not, therefore, be used in further assays. The host laboratory created a new transgenic mouse which expresses a fusion protein containing CD2/CD52 epitopes under the control of the foxP3 gene promoter. This means that any newly generated T-Reg cell can be instantly identified by its expression of CD2/CD52 protein on the cell surface. Moreover, existing monoclonal antibodies to CD52 (CAMPATH-1) or CD2 will be used to ablate T- Reg cells at any stage of an immune response to any given stimulus, e.g. transplanted tissues. These transgenic mice therefore provide a powerful research tool to investigate the roles of T-Reg cells actually in vivo