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| Status |
Public on Feb 09, 2006 |
| Title |
A function for interleukin 2 in Foxp3-expressing regulatory T cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Regulatory T cells (Treg cells) expressing the forkhead family transcription factor Foxp3 are critical mediators of dominant immune tolerance to self. Most Treg cells constitutively express the high-affinity interleukin 2 (IL-2) receptor alpha-chain (CD25); however, the precise function of IL-2 in Treg cell biology has remained controversial. To directly assess the effect of IL-2 signaling on Treg cell development and function, we analyzed mice containing the Foxp3gfp knock-in allele that were genetically deficient in either IL-2 (Il2-/-) or CD25 (Il2ra-/-). We found that IL-2 signaling was dispensable for the induction of Foxp3 expression in thymocytes from these mice, which indicated that IL-2 signaling does not have a nonredundant function in the development of Treg cells. Unexpectedly, Il2-/- and Il2ra-/- Treg cells were fully able to suppress T cell proliferation in vitro. In contrast, Foxp3 was not expressed in thymocytes or peripheral T cells from Il2rg-/- mice. Gene expression analysis showed that IL-2 signaling was required for maintenance of the expression of genes involved in the regulation of cell growth and metabolism. Thus, IL-2 signaling seems to be critically required for maintaining the homeostasis and competitive fitness of Treg cells in vivo.
Keywords: cell type comparison
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| Overall design |
We isolated Foxp3+ CD4+ T cells from Il2-/- mice treated with PBS or recombinant IL-2 for gene expression analysis using whole-genome oligonucleotide microarrays. To identify gene expression changes resulting from IL-2 deficiency and subsequent IL-2 stimulation in Treg cells, we directly compared expression profiles with each other and with expression profiles of Foxp3+ CD4+ T cells isolated from wild-type mice.
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| Contributor(s) |
Fontenot JD, Rasmussen JP, Gavin MA, Rudensky AY |
| Citation(s) |
16227984 |
| Submission date |
Feb 03, 2006 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Jeffrey Rasmussen |
| E-mail(s) |
rasmuss@u.washington.edu
|
| Phone |
2065439058
|
| Organization name |
University of Washington
|
| Department |
Immunology
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| Lab |
Rudensky
|
| Street address |
|
| City |
Seattle |
| State/province |
WA |
| ZIP/Postal code |
98195 |
| Country |
USA |
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| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (5)
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| Relations |
| BioProject |
PRJNA94983 |
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