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Updated: Jul 17, 2026

In Vitro Differentiation of Human CD4+FOXP3+ Induced Regulatory T Cells (iTregs) from Naïve CD4+ T Cells Using a TGF-β-containing Protocol
Published on: December 30, 2016
Maintenance of the Foxp3-dependent developmental program in mature regulatory T cells requires continued expression
Luke M Williams1, Alexander Y Rudensky
1Department of Immunology, University of Washington, Seattle, Washington 98195, USA.
The transcription factor Foxp3 is required for the development of regulatory T cells (T(reg) cell). Here we report that induced ablation of a loxP-flanked Foxp3 allele in mature T(reg) cells resulted in the loss of their suppressive function in vivo and acquisition of the ability to produce interleukin 2 and T helper type 1 cytokines. Furthermore, after adoptive transfer in the absence of functional T(reg) cells into lymphopenic hosts, T(reg) cells with deletion of Foxp3 proliferated and were predominant among tissue-infiltrating T cells. In agreement with those results, we found deregulation of Foxp3 target gene expression after Foxp3 deletion. Thus, continued Foxp3 expression in mature T(reg) cells is needed to maintain the transcriptional and functional program established during T(reg) cell development.
The transcription factor Foxp3 is required for the development of regulatory T cells (T(reg) cell). Here we report that induced ablation of a loxP-flanked Foxp3 allele in mature T(reg) cells resulted in the loss of their suppressive function in vivo and acquisition of the ability to produce interleukin 2 and T helper type 1 cytokines. Furthermore, after adoptive transfer in the absence of functional T(reg) cells into lymphopenic hosts, T(reg) cells with deletion of Foxp3 proliferated and were predominant among tissue-infiltrating T cells. In agreement with those results, we found deregulation of Foxp3 target gene expression after Foxp3 deletion. Thus, continued Foxp3 expression in mature T(reg) cells is needed to maintain the transcriptional and functional program established during T(reg) cell development.
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