T-regulatory cells (Tregs) play a fundamental role in the creation and maintenance of peripheral tolerance. Deficits in the numbers and/or function of Tregs may be an underlying cause of human autoimmune diseases including type 1 Diabetes Mellitus (T1D), whereas an over-abundance of Tregs can hinder immunity against cancer or pathogens. The importance of Tregs in the control of autoimmunity is well established in a variety of experimental animal models. In mice, manipulating the numbers and/or function of Tregs can decrease pathology in a wide range of contexts, including autoimmunity and it is widely assumed that similar approaches will be possible in humans. T1D, the most prevalent human autoimmune disease, has been a focus of interventions either through direct and indirect in vivo proliferations or through adoptive transfer of the in vitro generated antigen specific and non specific Treg. Some challenges still need to be addressed, including a more specific phenotype marker for Tregs; the reproducibility of satisfactory animal results in human and the reconcile of discrepancies between in vitro and in vivo studies. In this article, we will highlight the role of Tregs in autoimmune disease in general with a special focus on T1D, highlighting progress made and challenges ahead in developing Treg-based therapies.
