Cited by 1,819T-cell and B-cell ImmunologyPsoriasis: Treatment and PathogenesisIL-33, ST2, and ILC Pathways

A function for interleukin 2 in Foxp3-expressing regulatory T cells

Fontenot, Jason D, Rasmussen, Jeffrey P, Gavin, Marc A, Rudensky, Alexander Y·2005·Nature Immunology

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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Crossref · 10.1038/ni1263

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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.”

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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

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