Maintenance of the Foxp3-dependent developmental program in mature regulatory T cells requires continued expression of Foxp3.
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.
Williams
Luke M
LM
Department of Immunology, University of Washington, Seattle, Washington 98195, USA.
Rudensky
Alexander Y
AY
D019264:Adoptive Transfer; D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D019070:Cell Lineage; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology* / Q000378:metabolism; D015870:Gene Expression / Q000276:immunology; D020869:Gene Expression Profiling; D051379:Mice; D008822:Mice, Transgenic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017634:Self Tolerance / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse