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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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 [8]
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c-Rel-Dependent Priming of Naive T Cells by Inflammatory Cytokines
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Adipose Tissue Inflammation Induces B Cell Inflammation and Decreases B Cell Function in Aging
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Aged-related shifts in T cell homeostasis lead to intrinsic T cell defects
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Self-citationAging of the CD4 T Cell Compartment
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Self-citationMitochondrial Metabolism in T Cell Activation and Senescence: A Mini-Review
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Immunosenescence and organ transplantation
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Impact of Patient Age on Clinical Efficacy and Toxicity of Checkpoint Inhibitor Therapy
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Preventing or Reversing Immunosenescence: Can Exercise be an Immunotherapy?
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CD8 T cell responses to influenza virus infection in aged mice
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Immune memory and aging: an infinite or finite resource?
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Optimization of Immunotherapy in Elderly Cancer Patients
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Bim Dictates Naive CD4 T Cell Lifespan and the Development of Age-Associated Functional Defects
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Self-citationAn IL-7 Fusion Protein That Shows Increased Thymopoietic Ability
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Aging Augments IL-17 T-cell Alloimmune Responses
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Self-citationAging and Options to Halt Declining Immunity to Virus Infections
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Thymic Involution: Where Endocrinology Meets Immunology
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Effect of age on susceptibility to Salmonella Typhimurium infection in C57BL/6 mice
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Impact of immunosenescence on transplant outcome
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The effect of aging on cognate function and development of immune memory
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Self-citationAge effects on mouse and human B cells
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- 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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