Restoring Regulatory T Cells in Type 1 Diabetes

Genetic and cellular studies of type 1 diabetes in patients and in the nonobese diabetic mouse model of type 1 diabetes point to an imbalance between effector T cells and regulatory T cells (Tregs) as a driver of the disease. The imbalance may arise as a consequence of genetically encoded defects in thymic deletion of islet antigen-specific T cells, induction of islet antigen-specific thymic Tregs, unfavorable tissue environment for peripheral Treg induction, and failure of islet antigen-specific Tregs to survive in the inflamed islets secondary to insufficient IL-2 signals. These understandings are the foundation for rationalized design of new therapeutic interventions to restore the balance by selectively targeting effector T cells and boosting Tregs.