Grant: Doctoral: Vanier Canada Graduate Scholarships

Type 1 diabetes mellitus (T1DM) is an autoimmune disease in which insulin-secreting cells are destroyed by a type of white blood cell of the immune system called a T cell. People suffering from T1DM must receive insulin injections to maintain proper blood sugar levels. However, some patients can undergo an experimental procedure which involves transplanting the patient with insulin-secreting cells. While transplantation often frees the patient from requiring insulin injections, the patient must take expensive and harmful drugs to prevent his or her own immune system from rejecting the grafted cells. Thus, methods to achieve long-term graft survival that minimize the need for these drugs are desired. T regulatory (Treg) cells are a type of white blood cell with the ability to suppress immune responses. Therefore, these cells have great potential for use in transplantation to protect grafted cells from rejection. Our lab has developed a method to change human T cells into Treg cells by causing T cells to make a protein called FOXP3. The ability to generate Treg cells from T cells is important because greater numbers are required for therapies than the number of Treg cells found in human blood. The goals of this research project are to generate human Treg cells and to test the ability of these cells to inhibit graft rejection in a cross-species mouse model. In this model, mice that lack their own immune system are transplanted with human insulin-secreting cells. Next, they are injected with human blood cells which cause rejection of the grafts, mimicking rejection observed in transplant patients. We predict that injecting generated human Treg cells will inhibit rejection and allow long-term survival of transplanted cells. Successful generation of Treg cells that eliminate graft rejection in this model would indicate a promising future for clinical use of Treg cells, potentially reducing the need for harmful drugs and improving the health of transplant patients.