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Dramatic increase in naïve T cell turnover is linked to loss of naïve T cells from old primates
Open accessAbstract
The loss of naïve T cells is a hallmark of immune aging. Although thymic involution is a primary driver of this naïve T cell loss, less is known about the contribution of other mechanisms to the depletion of naïve T cells in aging primates. We examined the role of homeostatic cycling and proliferative expansion in different T cell subsets of aging rhesus macaques (RM). BrdU incorporation and the expression of the G 1 -M marker Ki-67 were elevated in peripheral naïve CD4 and even more markedly in the naïve CD8 T cells of old, but not young adult, RM. Proliferating naïve cells did not accumulate in old animals. Rather, the relative size of the naïve CD8 T cell compartment correlated inversely to its proliferation rate. Likewise, T cell receptor diversity decreased in individuals with elevated naïve CD8 T cell proliferation. This apparent contradiction was explained by a significant increase in turnover concomitant with the naïve pool loss. The turnover increased exponentially when the naïve CD8 T cell pool decreased below 4% of total blood CD8 cells. These results link the shrinking naïve T cell pool with a dramatic increase in homeostatic turnover, which has the potential to exacerbate the progressive exhaustion of the naïve pool and constrict the T cell repertoire. Thus, homeostatic T cell proliferation exhibits temporal antagonistic pleiotropy, being beneficial to T cell maintenance in adulthood but detrimental to the long-term T cell maintenance in aging individuals.
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“Only in later life, naive CD8+ T cells accelerate their turnover”
From Successful and Maladaptive T Cell Aging (2017) · cites this paper as Cicin-Sain et al., 2007
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“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 Cicin-Sain et al., 2007
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Self-citation
Metadata
- Authors
- Čičin-Šain, L., Messaoudi, I., Park, B., Currier, N., Planer, S., Fischer, M., Tackitt, S., Nikolich-Žugich, D., Legasse, A., Axthelm, M. K., Picker, L. J., Mori, M., & Nikolich-Žugich, J.
- Affiliations
- *Vaccine and Gene Therapy Institute and
- Oregon Health & Science University (US)
- Oregon National Primate Research Center (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2007-12-11
- Volume
- 104
- Issue
- 50
- Pages
- 19960-19965
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2148405
- OpenAlex
- W1995716646
- Cited by
- 129
- References
- 35
- Citations by year
- 2026: 2 · 2024: 1 · 2023: 5 · 2022: 5 · 2021: 8 · 2020: 2 · 2019: 8 · 2018: 6 · 2017: 9 · 2016: 8 · 2015: 6 · 2014: 12 · 2013: 11 · 2012: 9
- FWCI
- 3.24
- 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
- Deutsche Forschungsgemeinschaft
- U.S. Public Health Service
- Oregon National Primate Research Center
- National Institute on Aging (P01AG023664, U01AG021384)
- National Center for Research Resources (RR-0163, P51RR000163, K01RR000163)
- 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 › Virology › HIV Research and Treatment
- Keywords
- immunosenescence, naive T cells, T cell turnover, homeostatic proliferation, naive CD8+ T cells, naive CD4+ T cells, T cell receptor diversity, rhesus monkeys, Ki-67, antagonistic pleiotropy, thymic involution, T cell exhaustion
- MeSH terms
- Aging, Animals, Female, Homeostasis, Immunity, Innate, Immunologic Memory, Kinetics, Macaca mulatta, Male, T-Lymphocytes, Ki-67 Antigen, Cell Proliferation
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