Related Experiment Video
Updated: Jul 4, 2026
Adenoviral Transduction of Naive CD4 T Cells to Study Treg Differentiation
Published on: August 13, 2013
TGF-beta-induced Foxp3+ regulatory T cells rescue scurfy mice
Eva N Huter1, George A Punkosdy, Deborah D Glass
1Laboratory of Immunology, Cellular Immunology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Abstract:
Scurfy mice have a deletion in the forkhead domain of the forkhead transcription factor p3 (Foxp3), fail to develop thymic-derived, naturally occurring Foxp3+ regulatory T cells (nTreg), and develop a fatal lymphoproliferative syndrome with multi-organ inflammation. Transfer of thymic-derived Foxp3+ nTreg into neonatal Scurfy mice prevents the development of disease. Stimulation of conventional CD4+Foxp3(-) via the TCR in the presence of TGF-beta and IL-2 induces the expression of Foxp3 and an anergic/suppressive phenotype. To determine whether the TGF-beta-induced Treg (iTreg) were capable of suppressing disease in the Scurfy mouse, we reconstituted newborn Scurfy mice with polyclonal iTreg. Scurfy mice treated with iTreg do not show any signs of disease and have drastically reduced cell numbers in peripheral lymph nodes and spleen in comparison to untreated Scurfy controls. The iTreg retained their expression of Foxp3 in vivo for 21 days, migrated into the skin, and prevented the development of inflammation in skin, liver and lung. Thus, TGF-beta-differentiated Foxp3+ Treg appear to possess all of the functional properties of thymic-derived nTreg and represent a potent population for the cellular immunotherapy of autoimmune and inflammatory diseases.
Insights
Regulatory T cells (Tregs) are crucial for immune balance. This study shows that TGF-beta-induced Tregs can prevent fatal autoimmune disease in mice, offering potential for immunotherapy.
Area of Science:
- Immunology
- Cellular and Molecular Immunology
- Autoimmunity
Background:
- Scurfy mice exhibit a fatal lymphoproliferative syndrome due to a Foxp3 gene deletion, preventing regulatory T cell (Treg) development.
- Naturally occurring Tregs (nTregs) derived from the thymus can prevent this disease when transferred into neonatal Scurfy mice.
Purpose of the Study:
- To investigate if TGF-beta-induced Tregs (iTregs) can suppress the autoimmune disease in Scurfy mice.
- To assess the in vivo function and persistence of iTregs in a disease model.
Main Methods:
- Newborn Scurfy mice were reconstituted with polyclonal iTregs generated in vitro.
- Disease development, cell numbers, Foxp3 expression, and inflammation in various organs were monitored.
Main Results:
- Scurfy mice treated with iTregs showed no signs of disease and had reduced peripheral cell expansion compared to controls.
- iTregs maintained Foxp3 expression in vivo for at least 21 days.
- iTregs migrated to affected tissues and prevented inflammation in the skin, liver, and lungs.
Conclusions:
- TGF-beta-differentiated iTregs possess functional properties similar to thymic-derived nTregs.
- iTregs represent a promising cellular immunotherapy for autoimmune and inflammatory diseases.
