The study investigates the role of Foxp3+ regulatory T cells (Treg cells) in immune homeostasis and autoimmunity using a novel BAC-transgenic mouse model called "depletion of regulatory T cell" (DEREG) mice. These mice express a diphtheria toxin (DT) receptor-enhanced green fluorescent protein (eGFP) fusion protein under the foxp3 gene locus, allowing selective depletion of Foxp3+ Treg cells by DT injection. Key findings include: 1. **Generation of DERE G Mice**: DERE G mice were generated by introducing a DTR-eGFP fusion gene into the foxp3 locus using bacterial artificial chromosomes (BACs). The transgene was specifically expressed in Foxp3+CD4+ T cells, as confirmed by flow cytometry and histological analysis. 2. **DT Injection for Selective Depletion**: DT injection in DERE G mice efficiently depleted Foxp3+ Treg cells without affecting other lymphocyte subsets, demonstrating the specificity of the approach. 3. **Enhanced DTH Response**: Depletion of Foxp3+ Treg cells in DERE G mice led to an enhanced delayed-type hypersensitivity (DTH) response, suggesting that these cells play a crucial role in regulating local inflammatory responses. 4. **Scurfy-like Symptoms in Neonatal Mice**: Neonatal DERE G mice treated with DT showed scurfy-like symptoms, including splenomegaly, lymphadenopathy, insulitis, and severe skin inflammation, similar to those observed in scurfy mice. This indicates that the absence of functional Foxp3+ Treg cells is sufficient to induce a scurfy-like phenotype. 5. **Conclusion**: The study provides experimental evidence that Foxp3+ Treg cells are essential for maintaining immune homeostasis and preventing autoimmune diseases. The DERE G mouse model offers a powerful tool for further investigating the function of Treg cells in various immune responses and diseases.The study investigates the role of Foxp3+ regulatory T cells (Treg cells) in immune homeostasis and autoimmunity using a novel BAC-transgenic mouse model called "depletion of regulatory T cell" (DEREG) mice. These mice express a diphtheria toxin (DT) receptor-enhanced green fluorescent protein (eGFP) fusion protein under the foxp3 gene locus, allowing selective depletion of Foxp3+ Treg cells by DT injection. Key findings include: 1. **Generation of DERE G Mice**: DERE G mice were generated by introducing a DTR-eGFP fusion gene into the foxp3 locus using bacterial artificial chromosomes (BACs). The transgene was specifically expressed in Foxp3+CD4+ T cells, as confirmed by flow cytometry and histological analysis. 2. **DT Injection for Selective Depletion**: DT injection in DERE G mice efficiently depleted Foxp3+ Treg cells without affecting other lymphocyte subsets, demonstrating the specificity of the approach. 3. **Enhanced DTH Response**: Depletion of Foxp3+ Treg cells in DERE G mice led to an enhanced delayed-type hypersensitivity (DTH) response, suggesting that these cells play a crucial role in regulating local inflammatory responses. 4. **Scurfy-like Symptoms in Neonatal Mice**: Neonatal DERE G mice treated with DT showed scurfy-like symptoms, including splenomegaly, lymphadenopathy, insulitis, and severe skin inflammation, similar to those observed in scurfy mice. This indicates that the absence of functional Foxp3+ Treg cells is sufficient to induce a scurfy-like phenotype. 5. **Conclusion**: The study provides experimental evidence that Foxp3+ Treg cells are essential for maintaining immune homeostasis and preventing autoimmune diseases. The DERE G mouse model offers a powerful tool for further investigating the function of Treg cells in various immune responses and diseases.