Impact of age on T cell signaling: A general defect or specific alterations?
Abstract
Decreased immune responsiveness associated with aging is generally termed "immunosenescence". Several theories have been proposed to explain age-related declines in immune responses. Here, we will focus on and describe potential defects in T cell signal transduction from the membrane to the nucleus, leading to changes in the type, intensity and duration of the response as a major factor contributing to immunosenescence. We will first detail T cell signaling through the T cell receptor (TCR), CD28 and IL-2 receptor (IL-2R) and then discuss the observed age-related alterations to these signaling pathways. The role of membrane rafts in T cell signaling and T cell aging will be described. These factors will be considered in the context of the notion that age-related changes to T cell signaling may be attributed to changes in the functionality of the T cells due to shifts in T cell subpopulations with age. For this reason, we conclude by highlighting the application of multiparametric signaling analysis in leukocyte subsets using flow cytometry as a means to obtain a clearer picture with respect to age-related changes to immune signaling.
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CD4+ T cells show reduced T cell receptor signaling intensity and altered cytokine production after antigen binding.
“CD4 + T cells exhibit reduced T cell receptor signaling intensity and altered production of various cytokines following antigen binding (70,71).”
From Causes, consequences, and reversal of immune system aging (2013) · cites this paper as [71]
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Xu, Z., George, C., & Jolly, C. A. (2004) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2004.06.007 · Cited by 12 · see citing works
Impairment in a negative regulatory system for TCR signaling in CD4+ T cells from old mice
Inomata, M., Shimada, Y., Hayashi, M., Shimizu, J., & Ohno‐Iwashita, Y. (2007) · FEBS Letters · doi:10.1016/j.febslet.2007.05.063 · Cited by 8 · see citing works
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Causes, consequences, and reversal of immune system aging
Montecino-Rodriguez, E., Berent-Maoz, B., & Dorshkind, K. (2013) · Journal of Clinical Investigation · doi:10.1172/jci64096 · Cited by 793 · see citing works
Britanova, O. V., Putintseva, E. V., Shugay, M., Merzlyak, E. M., Turchaninova, M. A., Staroverov, D. B., Bolotin, D. A., Lukyanov, S., Bogdanova, E. A., Mamedov, I. Z., et al. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1302064 · Cited by 465 · see citing works
From “truly naïve” to “exhausted senescent” T cells: When markers predict functionality
Larbi, A., & Fulop, T. (2014) · Cytometry Part A · doi:10.1002/cyto.a.22351 · Cited by 359 · see citing works
Self-citationImmune aging, dysmetabolism, and inflammation in neurological diseases
Deleidi, M., Jäggle, M., & Rubino, G. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00172 · Cited by 260 · see citing works
Immune senescence, epigenetics and autoimmunity
Ray, D., & Yung, R. (2018) · Clinical Immunology · doi:10.1016/j.clim.2018.04.002 · Cited by 219 · see citing works
Cellular signaling in the aging immune system
Fulop, T., Le Page, A., Fortin, C., Witkowski, J. M., Dupuis, G., & Larbi, A. (2014) · Current Opinion in Immunology · doi:10.1016/j.coi.2014.05.007 · Cited by 158 · see citing works
Self-citationOn the immunological theory of aging
Fulop, T., Witkowski, J. M., Pawelec, G., Alan, C., & Larbi, A. (2014) · Interdisciplinary topics in gerontology and geriatrics · doi:10.1159/000358904 · Cited by 157 · see citing works
Self-citationNaive T cells: The crux of cellular immune aging?
Appay, V., & Sauce, D. (2014) · Experimental Gerontology · doi:10.1016/j.exger.2014.01.003 · Cited by 118 · see citing works
Beli, E., Clinthorne, J. F., Duriancik, D. M., Hwang, I., Kim, S., & Gardner, E. M. (2011) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2011.08.005 · Cited by 76 · see citing works
Le Page, A., Fortin, C., Garneau, H., Allard, N., Tsvetkova, K., Tan, C. T. Y., Larbi, A., Dupuis, G., & Fülöp, T. (2014) · Cell Communication and Signaling · doi:10.1186/1478-811x-12-2 · Cited by 44 · see citing works
Self-citationGardner, J. K., Mamotte, C. D. S., Jackaman, C., & Nelson, D. J. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2017.07.002 · Cited by 40 · see citing works
Age-associated alterations in inducible gene transcription in human CD4+ T lymphocytes
Bektas, A., Zhang, Y., Wood, W. H., Becker, K. G., Madara, K., Ferrucci, L., & Sen, R. (2013) · Aging · doi:10.18632/aging.100522 · Cited by 31 · see citing works
- Authors
- Larbi, A., Pawelec, G., Wong, S. C., Goldeck, D., Tai, J. J.-Y., & Fulop, T.
- Affiliations
- Agency for Science, Technology and Research (SG)
- University of Tübingen (DE)
- Venue
- Ageing Research Reviews
- Publisher
- Elsevier BV
- Published
- 2011-07
- Volume
- 10
- Issue
- 3
- Pages
- 370-378
- ISSN
- 1568-1637 (ISSN-L)
- OpenAlex
- W2054650629
- Cited by
- 108
- References
- 100
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 6 · 2023: 1 · 2022: 6 · 2021: 7 · 2020: 4 · 2019: 7 · 2018: 7 · 2017: 10 · 2016: 6 · 2015: 11 · 2014: 12 · 2013: 10 · 2012: 10
- FWCI
- 0.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Ageing Research Reviews (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Canadian Institutes of Health Research (63149)
- Biomedical Research Council
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- immunosenescence, T cell signaling, aging, T cell receptor signaling, CD28, interleukin-2 receptor, lipid rafts, T cell senescence, T cell subsets, age-related immune decline
- MeSH terms
- Aged, Aged, 80 and over, Aging, Homeostasis, Humans, T-Lymphocytes, Signal Transduction, Cellular Senescence, Membrane Microdomains
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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