T cell subset-specific susceptibility to aging
Open accessAbstract
With increasing age, the competence of the immune system to fight infections and tumors declines. Age-dependent changes have been mostly described for human CD8 T cells, raising the question of whether the response patterns for CD4 T cells are different. Gene expression arrays of memory CD4 T cells yielded a similar age-induced fingerprint as has been described for CD8 T cells. In cross-sectional studies, the phenotypic changes were not qualitatively different for CD4 and CD8 T cells, but occurred much more frequently in CD8 T cells. Homeostatic stability partially explained this lesser age sensitivity of CD4 T cells. With aging, naïve and central memory CD8 T cells were lost at the expense of phenotypically distinct CD8 effector T cells, while effector CD4 T cells did not accumulate. However, phenotypic shifts on central memory T cells were also more pronounced in CD8 T cells. This distinct stability in cell surface marker expression can be reproduced in vitro. The data show that CD8 T cells are age sensitive by at least two partially independent mechanisms: fragile homeostatic control and gene expression instability in a large set of regulatory cell surface molecules.
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Absolute numbers of naive CD4+ T cells in peripheral blood are stable in the elderly, while circulating naive CD8+ T cells progressively decline with age.
“Absolute numbers of naive CD4+ T cells in peripheral blood have been reported to be stable in the elderly. In contrast, circulating naive CD8+ T cells are progressively lost with age”
From Successful and Maladaptive T Cell Aging (2017) · cites this paper as Czesnikiewicz-Guzik et al., 2008
CD4 T cells age more slowly than CD8 T cells.
“CD4 T cells tend to age slower than their CD8 counterparts; the reason for this divergent behavior is not understood [16].”
From T-cell aging in rheumatoid arthritis (2014) · cites this paper as [16]
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- Authors
- Czesnikiewicz-Guzik, M., Lee, W.-W., Cui, D., Hiruma, Y., Lamar, D. L., Yang, Z.-Z., Ouslander, J. G., Weyand, C. M., & Goronzy, J. J.
- Affiliations
- Emory University (US)
- Mayo Clinic (US)
- Corresponding author
- Goronzy, Jörg J.
- Venue
- Clinical Immunology
- Publisher
- Elsevier BV
- Published
- 2008-04
- Volume
- 127
- Issue
- 1
- Pages
- 107-118
- ISSN
- 1521-6616 (ISSN-L)
- PMC
- PMC2435295
- OpenAlex
- W2035121127
- Cited by
- 478
- References
- 43
- Citations by year
- 2026: 25 · 2025: 34 · 2024: 33 · 2023: 35 · 2022: 35 · 2021: 32 · 2020: 28 · 2019: 22 · 2018: 22 · 2017: 27 · 2016: 26 · 2015: 21 · 2014: 23 · 2013: 19 · 2012: 21
- FWCI
- 10.43
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Clinical Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- Funders
- Mayo Foundation for Medical Education and Research
- National Institutes of Health (UL1TR000454)
- National Institute on Aging (R01AG015043, R01AG15043)
- National Institute of General Medical Sciences (T32GM008169)
- National Institute of Allergy and Infectious Diseases (R01 AI57266, U19AI057266)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR042527)
- National Center for Research Resources (M01-RR00039, M01RR000039)
- National Center for Advancing Translational Sciences
- 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
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- immunosenescence, CD8+ T cells, CD4+ T cells, T cell senescence, memory T cells, central memory T cells, effector T cells, T cell homeostasis, surface marker expression, age-related immune decline
- MeSH terms
- Adult, Aged, Aged, 80 and over, Aging, Female, Flow Cytometry, Homeostasis, Humans, Male, Middle Aged, Transcription, Genetic, CD4-Positive T-Lymphocytes, Immunophenotyping, T-Lymphocyte Subsets, CD8-Positive T-Lymphocytes, Oligonucleotide Array Sequence Analysis
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