Response to Comment on: Tritt et al. (2007) Functional Waning of Naturally Occurring CD4+ Regulatory T-Cells Contributes to the Onset of Autoimmune Diabetes: Diabetes 57:113–123, 2007

We thank Thomas et al. (1) for their insightful comments regarding the functional dynamics of CD4+Foxp3+ regulatory T-cells (Tregs) in their model of type 1 diabetes. An impressive array of studies in the literature establishes that CD4+Foxp3+ Tregs play a central, master-switch role in peripheral tolerance in the NOD mouse model of spontaneous type 1 diabetes (2,3). A central question is whether the onset of spontaneous disease in NOD mice results from a decline in regulation over time or from uncontrollable activity of self-reactive T-cells. Type 1 diabetes may reflect subtle, functional deficiencies in regulatory T-cells, thus allowing the diabetogenic process to unfold. In our study (4), we attempted to determine whether temporal, quantitative, or qualitative defects in CD4+Foxp3+ Tregs contribute to spontaneous type 1 diabetes. The BDC2.5 mouse model contains a highly pathogenic CD4+ T-cell repertoire and represents a unique system to study …