ABSTRACT
Foxp3⺠regulatory T (Treg) cells are critical contributors to the establishment and maintenance of immunological self-tolerance. Autoimmune type 1 diabetes (T1D) is characterized by the loss of self-tolerance to the insulin-producing ß cells in the pancreas and the destruction of ß cells, resulting in the development of chronic hyperglycemia at diagnosis. The application of strong agonistic T-cell receptor ligands provided under subimmunogenic conditions functions as a critical means for the efficient de novo conversion of naive CD4⺠T cells into Foxp3⺠Treg cells. The specific induction of Treg cells upon supply of strong-agonistic variants of certain self-antigens could therefore function as a critical instrument in order to achieve safe and specific prevention of autoimmunity such as T1D via the restoration of self-tolerance. Such immunotherapeutic strategies are being developed, and in the case of T1D aim to restrict autoimmunity and ß-cell destruction. In this review, we discuss the requirements and opportunities for Treg-based tolerance approaches with the goal of interfering with autoimmune T1D.
