CD4 T cell differentiation and regulation in autoimmune diabetes

Type 1 diabetes is an autoimmune disease in which cells of the immune system attack the pancreas and prevent it from producing insulin. Even if new insulin-producing cells are provided as a transplant, the immune system simply destroys these too. Medicines are available that suppress the entire immune system, but these have unwanted side effects. The key to successful treatment of type 1 diabetes is to pinpoint which cells cause disease so that these can be selectively targeted. We have performed a screen to characterise the immune cells that cause diabetes in a mouse model. This work has yielded a striking result; the cells are quite clearly a particular subset called follicular helper T cells. The possibility that this subset of immune cells could cause diabetes has not previously been explored. The proposed work seeks to investigate how these cells develop, and determine whether targeting this subset therapeutically can prevent or reverse diabetes. We will explore whether follicular helper T cells can be detected in blood samples from type 1 diabetes patients and will also take advantage of mouse diabetes models so we can test whether targeting these cells has beneficial effects.