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Ageing and life-long maintenance of T-cell subsets in the face of latent persistent infections.
Open accessAbstract
A diverse and well-balanced repertoire of T cells is thought to be crucial for the efficacious defence against infection with new or re-emerging pathogens throughout life. In the last third of the mammalian lifespan, the maintenance of a balanced T-cell repertoire becomes highly challenging because of the changes in T-cell production and consumption. In this Review, I question whether latent persistent pathogens might be key factors that drive this imbalance and whether they determine the extent of age-associated immune deficiency.
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“The impact of HIV disease on this process is not known, but emerging data suggest that these co-infections interact in a potential negative manner (41–44).”
From HIV and Aging: State of Knowledge and Areas of Critical Need for Research. A Report to the NIH Office of AIDS Research by the HIV and Aging Working Group (2012) · cites this paper as [41]
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Lee, K., Shin, K., Kim, G., Song, Y. C., Bae, E., Kim, I., Koh, C., & Kang, C. (2016) · Aging Cell · doi:10.1111/acel.12435 · Cited by 125
Physiology and pathology of T-cell aging
Minato, N., Hattori, M., & Hamazaki, Y. (2020) · International Immunology · doi:10.1093/intimm/dxaa006 · Cited by 124
CD8 T cells express randomly selected KIRs with distinct specificities compared with NK cells
Björkström, N. K., Béziat, V., Cichocki, F. M., Liu, L. L., Levine, J. J., Larsson, S., Koup, R. A., Anderson, S. K., Ljunggren, H., & Malmberg, K. (2012) · Blood · doi:10.1182/blood-2012-03-416867 · Cited by 119
Libri, V., Azevedo, R. I., Jackson, S. E., Di Mitri, D., Lachmann, R., Fuhrmann, S., Vukmanovic-Stejic, M., Yong, K., Battistini, L., Kern, F., et al. (2011) · Immunology · doi:10.1111/j.1365-2567.2010.03386.x · Cited by 111
Naive 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
Aravinthan, A., Pietrosi, G., Hoare, M., Jupp, J., Marshall, A., Verrill, C., Davies, S., Bateman, A., Sheron, N., Allison, M., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0072904 · Cited by 117
Age-related deregulation of naive T cell homeostasis in elderly humans
Ferrando‐Martínez, S., Ruíz-Mateos, E., Hernández, A., Gutiérrez, E., Rodríguez-Méndez, M. M., Ordóñez, A., & Leal, M. (2010) · AGE · doi:10.1007/s11357-010-9170-8 · Cited by 113
“The partial lymphopenia due to the loss of thymic function is believed to increase these proliferation rates (Kohler and Thiel, 2008; Nickolich-Zugich 2008).”
BackgroundThe aged tumor microenvironment limits T cell control of cancer
Chen, C.-Y., Jaiswal, S., Martínez, D., Yerinde, C., Ji, K. Y., Miranda, V., Fung, M. E., Weiss, S. A., Zschummel, M., Taguchi, K., et al. (2024) · Nature Immunology · doi:10.1038/s41590-024-01828-7 · Cited by 114
“Age-related defects in T cells include reduced naive T cell repertoire, telomere erosion, accumulated DNA damage and increased proinflammatory features 5–7 .”
T‐cell Immunoglobulin and ITIM Domain Contributes to CD 8+ T‐cell Immunosenescence
Song, Y., Wang, B., Song, R., Yu, H., Wang, D., Li, Y., Jiang, Y. Y., Xu, L., Ma, Y., Zheng, H., et al. (2018) · Aging Cell · doi:10.1111/acel.12716 · Cited by 109
“Immunosenescence is of high clinical relevance, as it contributes to multiple age-related comorbidities, including malignancies, infectious diseases, autoimmune diseases, and degenerative diseases (Gavazzi & Krause, 2002; Nikolich-Zugich, 2008).”
BackgroundLung innervation in the eye of a cytokine storm: neuroimmune interactions and COVID-19
Virgiliis, F. D., & Giovanni, S. D. (2020) · Nature Reviews Neurology · doi:10.1038/s41582-020-0402-y · Cited by 107
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“In parallel, T cells are under continuous stress through encountering new infections or controlling persistent and latent infections (3).”
Dysregulation of Systemic Immunity in Aging and Dementia
Lutshumba, J., Nikolajczyk, B. S., & Bachstetter, A. D. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.652111 · Cited by 104
“Latent persistent infections are also part of the secondary changes leading to immunesenescence (Nikolich-Zugich, 2008).”
BackgroundAge-related epithelial defects limit thymic function and regeneration
Kousa, A. I., Jahn, L., Zhao, K., Flores, A. E., Acenas, D. D., II, Lederer, E. E., Argyropoulos, K. V., Lemarquis, A. L., Granadier, D., Cooper, K., et al. (2024) · Nature Immunology · doi:10.1038/s41590-024-01915-9 · Cited by 116
“Consistent with its well-described decline in function over lifespan 2,3,21,22 , we found that total thymic cellularity declined in female mice across 18 months of age (Extended Data Fig.”
BackgroundGibson, S. E., & Hsi, E. D. (2009) · Human Pathology · doi:10.1016/j.humpath.2008.10.007 · Cited by 101
“This may include impaired effector B- and T-cell responses, decreased numbers of naive CD4- or CD8-positive T-cells, and loss of naive T-cell diversity [2,19-22].”
BackgroundInflammation, Aging, and Cancer: Tumoricidal Versus Tumorigenesis of Immunity
Khatami, M. (2009) · Cell Biochemistry and Biophysics · doi:10.1007/s12013-009-9059-2 · Cited by 100
Immune Aging and Rheumatoid Arthritis
Goronzy, J. J., Shao, L., & Weyand, C. M. (2010) · Rheumatic Disease Clinics of North America · doi:10.1016/j.rdc.2010.03.001 · Cited by 100
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Johnson, P. L. F., Yates, A. J., Goronzy, J. J., & Antia, R. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1209283110 · Cited by 94
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Moro‐García, M. A., Alonso‐Arias, R., López‐Vázquez, A., Suárez-García, F. M., Solano-Jaurrieta, J. J., Baltar, J., & López‐Larrea, C. (2011) · AGE · doi:10.1007/s11357-011-9240-6 · Cited by 94
“Naive T cells, which are needed to protect against new pathogens, are reduced in the elderly by several interrelated events: involution of the thymus, decline of naive T cells, reduction in T-cell repertoire diversity, and accumulation of memory T cells that are specific for persisting pathogens ( Nikolich-Zugich 2008…”
BackgroundBosch, J. A., Fischer, J. E., & Fischer, J. (2009) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2009.02.002 · Cited by 96
“The severe clinical complications of immunesenescence mark the terminal phase of a process that starts as early as adolescence (Akbar and Fletcher, 2005; Nikolich-Zugich, 2008).”
BackgroundT-Cell Biology in Aging, With a Focus on Lung Disease
Lee, N., Shin, M. S., & Kang, I. (2012) · The Journals of Gerontology Series A · doi:10.1093/gerona/glr237 · Cited by 89
Developmental dynamics of two bipotent thymic epithelial progenitor types
Nusser, A., Sagar, Swann, J. B., Krauth, B., Diekhoff, D., Calderón, L., Happe, C., Grün, D., & Boehm, T. L. J. (2022) · Nature · doi:10.1038/s41586-022-04752-8 · Cited by 89
Influenza-Induced Production of Interferon-Alpha is Defective in Geriatric Individuals
Canaday, D. H., Amponsah, N. A., Jones, L., Tisch, D. J., Hornick, T. R., & Ramachandra, L. (2010) · Journal of Clinical Immunology · doi:10.1007/s10875-010-9374-9 · Cited by 89
Metadata
- Authors
- Nikolich-Žugich, J.
- Venue
- Nature reviews. Immunology
- Published
- 2008-07
- Volume
- 8
- Issue
- 7
- Pages
- 512-522
- ISSN
- 1474-1733 (ISSN-L)
- 1474-1741
- PMC
- PMC5573867
- OpenAlex
- W1926141441
- Cited by
- 463
- References
- 128
- Citations by year
- 2026: 23 · 2025: 28 · 2024: 18 · 2023: 26 · 2022: 28 · 2021: 30 · 2020: 24 · 2019: 17 · 2018: 28 · 2017: 20 · 2016: 21 · 2015: 24 · 2014: 35 · 2013: 35 · 2012: 23
- FWCI
- 2.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature reviews. Immunology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (n01ai50027-8-0-1)
- U.S. Public Health Service (N01 50027)
- National Institute on Aging (AG 20719, AG23664, P01AG023664, AG 21384, R01AG020719, U01AG021384, R37AG020719)
- National Institute of Allergy and Infectious Diseases (N01 AI050027)
- 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 › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Keywords
- immunosenescence, T cell homeostasis, T cell subsets, persistent viruses, T cell receptor repertoire, aging
- MeSH terms
- Aging, Animals, Cell Differentiation, Herpes Simplex, Homeostasis, Humans, Infections, Receptors, Antigen, T-Cell, Thymus Gland, T-Lymphocyte Subsets, Cellular Senescence
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