Old mice accumulate activated effector CD4 T cells refractory to regulatory T cell-induced immunosuppression
Open accessAbstract
Chronic low-grade inflammation and reduced lymphocyte potency are implicated in the pathogenesis of major illnesses associated with aging. Whether this immune phenotype results from a loss of cell-mediated regulation or intrinsic dysregulated function of effector T cells (Teffs) requires further research. Here, we report that, as compared with young C57BL6 mice, old mice show an increased frequency of CD4+CD62L- Teffs with a dysregulated activated phenotype and markedly increased effector functions. Analysis of the frequency and suppressive function of CD4+FoxP3+ regulatory T cells (Tregs) indicates an increase in the frequency of FoxP3+ T cells with aging which, however, occurs within the CD4+CD25- T cells. Furthermore, whereas Tregs from young and old mice similarly suppress Teffs from young mice, both have a compromised suppressive capacity of Teffs from old mice, a phenomenon which is partially recovered in the presence of IL-2-producing CD4+CD62L+ non-Teffs. Finally, we observed that Teff subsets from old mice are enriched with IL-17A-producing T cells and exhibit intrinsically dysregulated expression of genes encoding cell-surface molecules and transcription factors, which play a key role in T-cell activation and regulation. We, thus, demonstrate an age-related impairment in the regulation of effector CD4 T cells, which may underlie the higher risk for destructive inflammation associated with aging.
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Previous studies on classical CD4 T cell subsets described reduced proliferation, lower IL-2 secretion, and accumulation of metabolic defects, along with higher production of pro-inflammatory mediators.
“For example, previous studies performed on classical CD4 T cell subsets described reduced proliferation, lower secretion of interleukin-2 (IL-2) cytokine (7, 8), and accumulation of metabolic defects (9), along with higher production of pro-inflammatory mediators (10).”
From Aging promotes reorganization of the CD4 T cell landscape toward extreme regulatory and effector phenotypes (2019) · cites this paper as [10]
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- Authors
- Harpaz, I., Bhattacharya, U., Elyahu, Y., Strominger, I., & Monsonego, A.
- Affiliations
- Ben-Gurion University of the Negev (IL)
- Corresponding author
- Monsonego, Alon
- Venue
- Frontiers in Immunology
- Publisher
- Frontiers Media SA
- Published
- 2017-03-22
- Volume
- 8
- Pages
- 283-283
- ISSN
- 1664-3224 (ISSN-L)
- PMC
- PMC5360761
- OpenAlex
- W2601638375
- Cited by
- 22
- References
- 62
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 1 · 2023: 3 · 2022: 3 · 2021: 3 · 2020: 3 · 2019: 5 · 2018: 1
- FWCI
- 1.10
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Immunology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Israel Science Foundation (531/11)
- 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 › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- aging, immunosenescence, CD4+ effector T cells, regulatory T cells, Foxp3, Treg suppressive function, L-selectin, interleukin-2, low-grade inflammation, T cell activation, T cell regulation, aged mice
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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