A function for interleukin 2 in Foxp3-expressing regulatory T cells
Abstract
Regulatory T cells (T(reg) cells) expressing the forkhead family transcription factor Foxp3 are critical mediators of dominant immune tolerance to self. Most T(reg) cells constitutively express the high-affinity interleukin 2 (IL-2) receptor alpha-chain (CD25); however, the precise function of IL-2 in T(reg) cell biology has remained controversial. To directly assess the effect of IL-2 signaling on T(reg) cell development and function, we analyzed mice containing the Foxp3(gfp) 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 T(reg) cells. Unexpectedly, Il2(-/-) and Il2ra(-/-) T(reg) 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 T(reg) cells in vivo.
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Treg cells in the periphery maintained their robust regulatory phenotype throughout the clinical trajectory of the patient.
“While Foxp3 expression was restored to baseline with mTORi-ICI combination, CD25 expression on Treg cells was only slightly modulated, indicating that TREG cells in the periphery maintained their robust regulatory phenotype throughout the clinical trajectory of the patient44.”
From Targeting the mTOR pathway uncouples the efficacy and toxicity of PD-1 blockade in renal transplantation (2019) · cites this paper as [44]
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- Authors
- Fontenot, J. D., Rasmussen, J. P., Gavin, M. A., & Rudensky, A. Y.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Fontenot, Jason D
- Rudensky, Alexander Y
- Venue
- Nature Immunology
- Published
- 2005-10-16
- Volume
- 6
- Issue
- 11
- Pages
- 1142-1151
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W2068639447
- Cited by
- 1,819
- References
- 40
- Citations by year
- 2026: 37 · 2025: 35 · 2024: 45 · 2023: 64 · 2022: 51 · 2021: 79 · 2020: 70 · 2019: 81 · 2018: 83 · 2017: 76 · 2016: 76 · 2015: 97 · 2014: 85 · 2013: 105 · 2012: 106
- FWCI
- 43.86
- Type
- journal article
- Language
- en
- Update notices
- erratum (2006-04-01)
- Open access
- closed
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (R01AI034206)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
- Keywords
- regulatory T cells, Foxp3, interleukin-2 signaling, IL-2 receptor alpha chain, CD25, IL-2 deficiency, IL-2 receptor gamma chain, T cell development, T cell suppression, immune tolerance, cellular metabolism
- MeSH terms
- Animals, Cell Differentiation, DNA-Binding Proteins, Gene Expression Regulation, Homeostasis, Immune Tolerance, Interleukin-2, Lymphocyte Activation, Mutation, T-Lymphocytes, Receptors, Interleukin-2, Signal Transduction, Green Fluorescent Proteins, Mice, Forkhead Transcription Factors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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