The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.
CD4 T cell memory derived from young naive cells functions well into old age, but memory generated from aged naive cells functions poorly
Open accessAbstract
Age-related declines in immune function have an impact on both primary and memory responses. In this study, we have examined the ability of naive CD4 T cells from young and aged T cell receptor transgenic mice to establish functional memory. We found that memory cells generated from young CD4 T cells responded well to antigen, even a year after generation, whereas memory cells derived from CD4 T cells from aged mice responded poorly both ex vivo and in vivo . Memory cells generated from aged naive cells proliferate less, produce reduced levels of cytokines, and exhibit reduced cognate helper function, compared with memory cells generated by using young naive cells. These results indicate that it is the age of the naive T cell when it first encounters antigen, rather than the age when it reencounters antigen, that is critical for good memory CD4 T cell function.
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“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 [8]
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Cites
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Age-related changes in lymphocyte development and function
Linton, P. J., & Dorshkind, K. A. (2004) · Nature Immunology · doi:10.1038/ni1033 · Cited by 1,199
The aging of the immune system
Weiskopf, D., Weinberger, B., & Grubeck-Loebenstein, B. (2009) · Transplant International · doi:10.1111/j.1432-2277.2009.00927.x · Cited by 908
How the ageing microenvironment influences tumour progression
Fane, M., & Weeraratna, A. T. (2020) · Nature Reviews Cancer · doi:10.1038/s41568-019-0222-9 · Cited by 849
Gruver, A., Hudson, L., & Sempowski, G. (2007) · The Journal of Pathology · doi:10.1002/path.2104 · Cited by 834
“Following in vitro or in vivo stimulation with pigeon cytochrome c, naı̈ve T cells from aged mice exhibited reduced activation, differentiation and cytokine production [89,90].”
BackgroundMethodResultInfluentialA B-cell subset uniquely responsive to innate stimuli accumulates in aged mice
Hao, Y., O'Neill, P., Naradikian, M. S., Scholz, J. L., & Cancro, M. P. (2011) · Blood · doi:10.1182/blood-2011-01-330530 · Cited by 622
Metadata
- Authors
- Haynes, L., Eaton, S. M., Burns, E. M., Randall, T. D., & Swain, S. L.
- Affiliations
- Trudeau Institute (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2003-12
- Volume
- 100
- Issue
- 25
- Pages
- 15053-15058
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC299903
- OpenAlex
- W2091101346
- Cited by
- 270
- References
- 33
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 5 · 2023: 10 · 2022: 9 · 2021: 27 · 2020: 11 · 2019: 14 · 2018: 12 · 2017: 14 · 2016: 10 · 2015: 7 · 2014: 9 · 2013: 22 · 2012: 9
- FWCI
- 2.80
- 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 Institute on Aging (P01AG021600, P01AG001743, R01AG021054, AG21054, AG-01743)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- CD4+ T cell memory, naive T cells, immunosenescence, aging, T cell receptor transgenic mice, cytokine production, T cell proliferation, helper functions
- MeSH terms
- Aging, Animals, Cell Line, Cell Separation, Flow Cytometry, Immunologic Memory, Interferon-gamma, Interleukin-2, Lymphocytes, Mice, Transgenic, Microscopy, Fluorescence, Phenotype, CD4-Positive T-Lymphocytes, Interleukin-4, Interleukin-5, Cytokines, Cell Culture Techniques, Mice
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