The Influence of Age on T Cell Generation and TCR Diversity
Open accessAbstract
The ability to mount protective immune responses depends on the diversity of T cells. T cell diversity may be compromised by the declining thymic output of new T cells. The aging process imposes a threat to diversity, because thymic function deteriorates. In this study we have examined the relationship between thymic production, homeostatic T cell proliferation and TCR β-chain diversity in young (∼25 years), middle-aged (∼60 years), and elderly adults (∼75 years). TCR excision circles (TREC) as a marker of thymic output exponentially decreased by >95% between 25 and 60 years of age. The frequency of Ki67+ cycling CD4 T cells remained steady, and surprisingly, the diversity of the naive CD4 T cell repertoire was maintained at ∼2 × 107 different TCR β-chains. After the age of 70 years, TRECs only slightly declined, but homeostatic proliferation doubled. The diversity of the T cell pool drastically contracted to 200,000 TCR β-chains. Also, the phenotypic distinction between naive and memory CD4 T cells became fuzzy. The collapse in CD4 T cell diversity during the seventh and eighth decades indicates substantial T cell loss and implies that therapeutic measures to improve vaccine responses will have to include strategies for T cell replenishment.
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Daily turnover of naive CD4+ and CD8+ T cells remains stable at about 0.04% throughout adulthood, with no apparent compensatory increase in homeostatic proliferation with age.
“Daily turnover rates of naive CD4+ and CD8+ T cells are stable throughout adulthood at about 0.04%, with no apparent need for compensatory increase in homeostatic proliferation with age.”
From Successful and Maladaptive T Cell Aging (2017) · cites this paper as Naylor et al., 2005
In later life, naive CD8+ T cells accelerate turnover.
“Only in later life, naive CD8+ T cells accelerate their turnover”
From Successful and Maladaptive T Cell Aging (2017) · cites this paper as Naylor et al., 2005
Early studies found clonal populations within naive cells after age 60.
“Early studies described clonal populations within naive cells after the age of 60 years”
From Successful and Maladaptive T Cell Aging (2017) · cites this paper as Naylor et al., 2005
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- Authors
- Naylor, K., Li, G., Vallejo, A. N., Lee, W.-W., Koetz, K., Bryl, E., Witkowski, J., Fulbright, J., Weyand, C. M., & Goronzy, J. J.
- Affiliations
- Mayo Clinic (US)
- Department of Medicine, Mayo Clinic and Graduate School , Rochester, MN 55905
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-06-01
- Volume
- 174
- Issue
- 11
- Pages
- 7446-7452
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1556334181
- Cited by
- 802
- References
- 2
- Citations by year
- 2026: 27 · 2025: 29 · 2024: 19 · 2023: 37 · 2022: 38 · 2021: 46 · 2020: 53 · 2019: 46 · 2018: 39 · 2017: 51 · 2016: 35 · 2015: 42 · 2014: 43 · 2013: 45 · 2012: 54
- FWCI
- 10.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (R01AG015043, AG 15043)
- National Institute of Allergy and Infectious Diseases (AI 57266, U19AI057266)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- immunosenescence, T cell senescence, thymic output, TREC, homeostatic proliferation, naive CD4+ T cells, memory T cells, vaccine response in the elderly
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Aging, Cell Differentiation, Homeostasis, Humans, Immunologic Memory, Middle Aged, Receptors, Antigen, T-Cell, Thymus Gland, Gene Rearrangement, beta-Chain T-Cell Antigen Receptor, CD4-Positive T-Lymphocytes, T-Lymphocyte Subsets, Resting Phase, Cell Cycle, Cell Proliferation
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