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Are senescence and exhaustion intertwined or unrelated processes that compromise immunity?
Abstract
Can the immune system be reactivated continuously throughout the lifetime of an organism or is there a finite point at which repeated antigenic challenge leads to the loss of lymphocyte function or the cells themselves or both? Replicative senescence and exhaustion are processes that control T cell proliferative activity and function; however, there is considerable confusion over the relationship between these two intrinsic cellular control mechanisms. In this Opinion article, we compare the molecular regulation of senescence and exhaustion in T cells. Available data suggest that both processes are regulated independently of each other and that it may be safer to block exhaustion than senescence to enhance immunity.
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“In addition to phenotypic alteration, senescent T cells manifest defective killing abilities and the development of negative regulatory functions [52,53].”
From T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment (2013) · cites this paper as [53]
In the citing paper
“Based on phenotype and function, senescent T cells must not be confused with exhausted T cells induced by prolonged antigen stimulation [40–42].”
From T-cell aging in rheumatoid arthritis (2014) · cites this paper as [42]
In the citing paper
“The restriction to the extent of proliferation of T cells, especially those that are specific for frequently encountered or persistent antigens may therefore compromise the maintenance of specific immunity in older humans as they may be driven towards senescence [1, 12].”
From Senescence of T Lymphocytes: Implications for Enhancing Human Immunity (2016) · cites this paper as [12]
In the citing paper
“Short telomeres are interpreted as DNA damage by cell sensing machinery that initiates a cascade of events that culminates in growth arrest (reviewed in Akbar and Henson 2011 [12]).”
From Senescence of T Lymphocytes: Implications for Enhancing Human Immunity (2016) · cites this paper as [12]
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“; https://doi.org/10.1101/2023.01.16.23284612doi: medRxiv preprint terminal differentiation and are associated with the senescence profile of T lymphocytes 338 (Akbar & Henson, 2011; Pangrazzi & Weinberger, 2020).”
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Oral administration of Lactobacillus kefiri Fanghua reduces immune senescence and aging phenotypes
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“Senescence can be induced as the result of telomere shortening or non-telomeric DNA damage (Akbar and Henson, 2011), both of which have been reported to occur in smokers (Song et al., 2010; Valdes et al., 2005).”
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“…have demonstrated that aging T cells frequently exhibit elevated markers of activation (HLA-DR, CD25), exhaustion (PD-1, TIGIT), and occasionally express NK-like receptors, features typically associated with senescence-like or terminal differentiation (Goronzy & Weyand, 2019; Akbar & Henson, 2011).”
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Metadata
- Authors
- Akbar, A. N., & Henson, S. M.
- Affiliations
- University College London (GB)
- Corresponding author
- Akbar, Arne N.
- ORCID
- Akbar, Arne N.
- Venue
- Nature Reviews Immunology
- Published
- 2011-03-25
- Volume
- 11
- Issue
- 4
- Pages
- 289-295
- ISSN
- 1474-1733 (ISSN-L)
- 1474-1741
- OpenAlex
- W2068367301
- Cited by
- 474
- References
- 96
- Citations by year
- 2026: 36 · 2025: 41 · 2024: 28 · 2023: 28 · 2022: 38 · 2021: 36 · 2020: 33 · 2019: 32 · 2018: 31 · 2017: 20 · 2016: 33 · 2015: 32 · 2014: 26 · 2013: 29 · 2012: 20
- FWCI
- 2.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature reviews. Immunology (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Wellcome Trust
- Biotechnology and Biological Sciences Research Council
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- T cell senescence, T cell exhaustion, replicative senescence, viral persistence, aging, immune reactivation, T cell proliferation, immunosenescence
- MeSH terms
- Animals, Fatigue, Humans, Immunity, Cellular, Lymphocyte Activation, T-Lymphocytes, Virus Diseases, Cellular Senescence, Mice
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