Alteration of Regulatory T Cells in Type 1 Diabetes Mellitus: A Comprehensive Review

Type 1 diabetes mellitus (T1DM) is a T cell-mediated autoimmune disease characterized by the destruction of pancreatic beta cells. Numerous studies have demonstrated the key role of CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs) in the development of T1DM. However, the changes in Treg expression and function as well as the regulation of these activities are not clearly elucidated. Most studies on the role of Tregs in T1DM were performed on peripheral blood rather than pancreas or pancreatic lymph nodes. Tissue-based studies are more difficult to perform, and there is a lack of histological data to support the role of Tregs in T1DM. In spite of this, strategies to increase Treg cell number and/or function have been viewed as potential therapeutic approaches in treating T1DM, and several clinical trials using these strategies have already emerged. Notably, many trials fail to demonstrate clinical response even when Treg treatment successfully boosts Tregs. In view of this, whether a failure of Tregs does exist and contribute to the development of T1DM and whether more Tregs would be clinically beneficial to patients should be carefully taken into consideration before applying Tregs as treatments in T1DM.