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Metabolic reprogramming of human CD8+ memory T cells through loss of SIRT1
Open accessAbstract
The expansion of CD8+CD28– T cells, a population of terminally differentiated memory T cells, is one of the most consistent immunological changes in humans during aging. CD8+CD28– T cells are highly cytotoxic, and their frequency is linked to many age-related diseases. As they do not accumulate in mice, many of the molecular mechanisms regulating their fate and function remain unclear. In this paper, we find that human CD8+CD28– T cells, under resting conditions, have an enhanced capacity to use glycolysis, a function linked to decreased expression of the NAD+-dependent protein deacetylase SIRT1. Global gene expression profiling identified the transcription factor FoxO1 as a SIRT1 target involved in transcriptional reprogramming of CD8+CD28– T cells. FoxO1 is proteasomally degraded in SIRT1-deficient CD8+CD28– T cells, and inhibiting its activity in resting CD8+CD28+ T cells enhanced glycolytic capacity and granzyme B production as in CD8+CD28– T cells. These data identify the evolutionarily conserved SIRT1–FoxO1 axis as a regulator of resting CD8+ memory T cell metabolism and activity in humans.
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“This cell population is characterized by decreased SIRT1 and FOXO1 levels, resulting in an enhanced glycolytic capacity and granzyme B production116.”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [116]
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Metadata
- Authors
- Jeng, M. Y., Hull, P. A., Fei, M., Kwon, H.-S., Tsou, C.-L., Kasler, H., Ng, C.-P., Gordon, D. E., Johnson, J., Krogan, N., Verdin, E., & Ott, M.
- Affiliations
- Gladstone Institutes (US)
- Gladstone Institutes, San Francisco, CA 1
- ORCID
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2017-11-30
- Volume
- 215
- Issue
- 1
- Pages
- 51-62
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC5748845
- OpenAlex
- W2771883021
- Cited by
- 121
- References
- 78
- Citations by year
- 2026: 12 · 2025: 14 · 2024: 3 · 2023: 15 · 2022: 17 · 2021: 20 · 2020: 17 · 2019: 16 · 2018: 6 · 2017: 1
- FWCI
- 6.61
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Journal of Experimental Medicine (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc-sa)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (P30 AI027763, 1DP1DA038043)
- James B. Pendleton Charitable Trust (NIH S10 RR028962)
- Gladstone Institutes
- National Science Foundation (1144247)
- Evangelische Studienwerk Villigst
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › FOXO transcription factor regulation
- Keywords
- CD8+CD28- T cells, SIRT1, FOXO1, metabolic reprogramming, glycolysis, memory T cells, aging, proteasomal degradation, granzyme B, cytotoxic T lymphocytes, NAD+-dependent deacetylase, transcriptional reprogramming
- MeSH terms
- Forkhead Box Protein O1, Cytotoxicity, Immunologic, Energy Metabolism, Gene Expression Regulation, Humans, Immunologic Memory, Biomarkers, T-Lymphocyte Subsets, CD28 Antigens, CD8-Positive T-Lymphocytes, Sirtuin 1
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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