Mice hemizygous for the BAC Foxp3DTR transgene are viable and fertile. These mice express a human heparin-binding EGF-like growth factor (HBEGF or DTR, diptheria toxin receptor) sequence fused to an enhanced green fluorescent protein (EGFP) directed by Foxp3 (forkhead box P3) promoter/enhancer regions on the BAC transgene. FOXP3 is a transcription factor necessary for the development and function of regulatory T (Treg) cells, which are required for suppression of self-reactive T cells and prevention of some autoimmune diseases. In these mice, EGFP expression is evident in FOXP3+ CD4+CD25+ Treg cells. Two consecutive daily injection of diptheria toxin (DT) specifically depletes 80%-90% of these cells in lymphoid organs such as the spleen, axillary lymph nodes (LN), and pancreatic LN. Three days after the last injection, Treg cell numbers recover to only 60% depletion. Pancreatic islets of the DT-injected mice show a strong immune infiltrate at day 12 after this treatment. In contrast, only mild infiltrates are evident at the same time point after injections every other day.
Foxp3DTR were bred to NOD.Cg-Tg(TcraBDC2.5,TcrbBDC2.5)1Doi/DoiJ mice (Stock No. 004460) in order to study the direct role of FOXP3+ Treg ablation on islet infiltration during the progression of autoimmune diabetes. Histological changes in islet morphology are seen as early as 24 hours after DT-induction. Overt disease develops within 3 days as evident by the activation of natural killer (NK) cells within the insulitic lesion, and the induction of Ifnγ expression.
