The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
Age-associated increase in lifespan of naive CD4 T cells contributes to T-cell homeostasis but facilitates development of functional defects
Open accessAbstract
With age, T-cell generation from the thymus is much reduced, yet a substantial naïve T-cell pool is maintained even in aged animals, suggesting that naïve T cells either persist longer or turn over faster to maintain T-cell homeostasis. We found that with age, naïve CD4 T cells became progressively longer-lived. Their longer lifespan did not depend on recognition of self-peptide/class II. Newly generated naïve T cells derived from aged stem cells had a shorter lifespan, like that of young naïve T cells. Conversely, naïve CD4 T cells derived from middle-aged thymectomized mice were longer-lived in vivo, and their development of functional defects was accelerated. These observations suggest that naïve T cells develop their longer lifespan during their sojourn in the periphery. Increased longevity of naïve CD4 T cells correlated well with reduced expression of proapoptotic molecule Bim. We suggest that the intrinsic increase in longevity helps maintain naïve T-cell homeostasis but facilitates the development of functional defects in mice.
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In the citing paper
“With aging, the naïve subset shrinks along with the accumulation of highly differentiated memory cells, which often show dysregulated properties (5, 6).”
From Aging promotes reorganization of the CD4 T cell landscape toward extreme regulatory and effector phenotypes (2019) · cites this paper as [6]
In the citing paper
“Age-associated functional changes in naive murine T cells are not a consequence of replication—they at most divide once throughout life—but are a corollary of cellular longevity that even increases after thymectomy or in aged mice”
From Successful and Maladaptive T Cell Aging (2017) · cites this paper as Tsukamoto et al., 2009
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ER Stress Triggers Apoptosis by Activating BH3-Only Protein Bim
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Age-related changes in lymphocyte development and function
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Maintaining the norm: T-cell homeostasis
Jameson, S. C. (2002) · Nature reviews. Immunology · doi:10.1038/nri853 · Cited by 597
Activated T Cell Death In Vivo Mediated by Proapoptotic Bcl-2 Family Member Bim
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The twilight of immunity: emerging concepts in aging of the immune system
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Thomas, R., Wang, W., & Su, D.-M. (2020) · Immunity & Ageing · doi:10.1186/s12979-020-0173-8 · Cited by 442
Successful and Maladaptive T Cell Aging
Goronzy, J. J., & Weyand, C. M. (2017) · Immunity · doi:10.1016/j.immuni.2017.03.010 · Cited by 362
Immune ageing at single-cell resolution
Mogilenko, D. A., Shchukina, I., & Artyomov, M. N. (2021) · Nature reviews. Immunology · doi:10.1038/s41577-021-00646-4 · Cited by 396
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Metadata
- Authors
- Tsukamoto, H., Clise-Dwyer, K., Huston, G. E., Duso, D. K., Buck, A. L., Johnson, L. L., Haynes, L., & Swain, S. L.
- Affiliations
- Trudeau Institute (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2009-10-27
- Volume
- 106
- Issue
- 43
- Pages
- 18333-18338
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2759371
- OpenAlex
- W2137105060
- Cited by
- 166
- References
- 47
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 4 · 2023: 7 · 2022: 9 · 2021: 21 · 2020: 8 · 2019: 2 · 2018: 7 · 2017: 14 · 2016: 9 · 2015: 15 · 2014: 16 · 2013: 12 · 2012: 11
- FWCI
- 4.03
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (AG021600)
- National Institute on Aging (P01AG021600, R37AG025805, AG021600, AG025805)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- naive CD4+ T cells, T cell lifespan, aging, T cell homeostasis, thymic output, thymectomy, building information modeling, apoptosis, periphery
- MeSH terms
- Bcl-2-Like Protein 11, Aging, Animals, Cell Survival, Histocompatibility Antigens, Homeostasis, Immunity, Innate, Membrane Proteins, Proto-Oncogene Proteins, Receptors, Antigen, T-Cell, T-Lymphocytes, Thymectomy, Signal Transduction, CD4-Positive T-Lymphocytes, Apoptosis Regulatory Proteins, Mice
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