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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“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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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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