Human memory T cells with a naive phenotype accumulate with aging and respond to persistent viruses
Open accessAbstract
The number of naive T cells decreases and susceptibility to new microbial infections increases with age. Here we describe a previously unknown subset of phenotypically naive human CD8(+) T cells that rapidly secreted multiple cytokines in response to persistent viral antigens but differed transcriptionally from memory and effector T cells. The frequency of these CD8(+) T cells, called 'memory T cells with a naive phenotype' (TMNP cells), increased with age and after severe acute infection and inversely correlated with the residual capacity of the immune system to respond to new infections with age. CD8(+) TMNP cells represent a potential new target for the immunotherapy of persistent infections and should be accounted for and subtracted from the naive pool if truly naive T cells are needed to respond to antigens.
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The increased turnover of naive CD8+ T cells in later life comes from CD95+CD45RA+CD28+ cells that are reverted memory cells, memory stem cells, or extensively homeostatically proliferated cells resembling murine virtual memory.
“This increased turnover does not derive from truly naive cells, but from CD95+CD45RA+CD28+ T cells that represent reverted memory cells (Pulko et al., 2016), memory stem cells (Fuertes Marraco et al., 2015), or cells that have undergone extensive homeostatic proliferation reminiscent of murine virtual memory cells”
From Successful and Maladaptive T Cell Aging (2017) · cites this paper as Pulko et al., 2016
Chromatin accessibility studies in ageing immune cells have demonstrated shifts in chromatin accessibility with age in CD8+ T cells.
“Chromatin accessibility studies in ageing immune cells have demonstrated shifts in chromatin accessibility with age in CD8+ T cells144–147.”
From Measuring biological age using omics data (2022) · cites this paper as [145]
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References 53 · Cited by 175
- Authors
- Pulko, V., Davies, J. S., Martinez, C., Lanteri, M. C., Busch, M. P., Diamond, M. S., Knox, K., Bush, E. C., Sims, P. A., Sinari, S., Billheimer, D., Haddad, E. K., Murray, K. O., Wertheimer, A. M., & Nikolich-Žugich, J.
- Affiliations
- University of Arizona (US)
- Blood Systems Research Institute (US)
- Washington University in St. Louis (US)
- Columbia University Irving Medical Center (US)
- Drexel University (US)
- Baylor College of Medicine (US)
- ORCID
- Venue
- Nature Immunology
- Published
- 2016-06-06
- Volume
- 17
- Issue
- 8
- Pages
- 966-975
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- PMC
- PMC4955715
- OpenAlex
- W2412807878
- Cited by
- 175
- References
- 53
- Citations by year
- 2026: 13 · 2025: 14 · 2024: 8 · 2023: 12 · 2022: 18 · 2021: 16 · 2020: 13 · 2019: 23 · 2018: 24 · 2017: 28 · 2016: 6
- FWCI
- 16.58
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (P30AG008017, R01AG048021)
- National Heart, Lung, and Blood Institute (RC2HL101632)
- National Cancer Institute (P30CA023074)
- National Institute of Environmental Health Sciences (P30ES006694)
- 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
- CD8+ T cells, T cell senescence, viral persistence, cytokine production, T cell receptor, immunosenescence
- MeSH terms
- Immunosenescence, Acute Disease, Adult, Aged, Aged, 80 and over, Aging, Cells, Cultured, Humans, Immunologic Memory, Lymphocyte Activation, Middle Aged, Phenotype, Virus Diseases, Immunophenotyping, T-Lymphocyte Subsets, CD8-Positive T-Lymphocytes, Young Adult, Transcriptome
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