Cited by 466T-cell and B-cell ImmunologyTelomeres, Telomerase, and SenescenceHIV Research and Treatment

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Ageing and life-long maintenance of T-cell subsets in the face of latent persistent infections.

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Nikolich-Žugich, Janko·2008·Nature reviews. Immunology

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Abstract

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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Background
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Background
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Background
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“The proportion of naïve (CD44low CD62Lhigh) cells has been shown to markedly decrease among CD4+ T cells, with an age-dependent increase in effector memory T cells (TEM: CD44high CD62Llow) [11,12].”
Background
Stem cell transplantation improves aging-related diseases
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“It is well established that the function of the immune system declines with age (34, 35).”
Background
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Background
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“In CD4+ T cells, the populations of naïve (CD44loCD62Lhi) T cells markedly decline in ontogeny, with age-dependent increases occurring in effector memory T cells (CD44hiCD62Llo) [30, 31].”
Background
Clinicopathological analysis of neoplastic PD-L1-positive EBV+ diffuse large B cell lymphoma, not otherwise specified, in a Japanese cohort
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Background
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Background
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Background
Descriptive epidemiology of infectious gastrointestinal illnesses in Sydney, Australia, 2007–2010
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BackgroundInfluential
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Background
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Background
Immune Cells and Immunosenescence
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“Rather, the immune dysregulation caused by this virus during a lifetime of reactivation [ 6 ] has been postulated to contribute to the exacerbation of autoimmunity.”
BackgroundInfluential
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“Possible mechanisms that have been described to be responsible for the expansion of the memory T cell pool include the dysregulation of IL-7Ra, an increased turnover rate of naïve T cells favoring their conversion into memory T cells as well as the increased availability of IL-7 or IL-15 as a consequence of a diminish…”
Background
Immunosenescence and Inflammaging in COVID-19
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“Moreover, as aging is associated with decreased T cell function ( Franceschi et al., 2000; Linton and Thoman, 2001; Miller, 1996; Nikolich-Zugich, 2008; Pawelec et al., 1999), older T cells may be less effective at protecting axotomized facial motor neurons.”
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Advanced biological age is associated with improved antibody responses in older high-dose influenza vaccine recipients over four consecutive seasons
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“For example, innate immune cells such as monocytes tend to exhibit a hyperinflammatory phenotype with reduced signalling capacity [10], while the proliferative capacity of T- and B-lymphocytes decline [11].”
Background
The immunosenescence clock: A new method for evaluating biological age and predicting mortality risk
Li, S., Wang, K., Wu, J., & Zhu, Y. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102653 · Cited by 18
“Persistent latent infections repeatedly stimulate the immune system throughout an individual ’ s life, affecting the phenotype and function of immune cells (Nikolich-Zugich, 2008).”
Workshop on Immunizations in Older Adults: Identifying Future Research Agendas
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“Reprinted with permission.(26) IMMUNIZATION AND AGING 767 JAGS APRIL 2010–VOL.”
Background
Premature thymic involution is independent of structural plasticity of the thymic stroma
Franckaert, D., Schlenner, S., Heirman, N., Gill, J. W., Skogberg, G., Ekwall, O., Put, K., Linterman, M. A., Dooley, J., & Liston, A. (2015) · European Journal of Immunology · doi:10.1002/eji.201445277 · Cited by 15
Donor Graft Cytomegalovirus Serostatus and the Risk of Arterial and Venous Thrombotic Events in Seronegative Recipients After Non-Thoracic Solid Organ Transplantation
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Immune Reconstitution Following Hematopoietic Cell Transplantation
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Analysis of cytomegalovirus-specific T-cell responses in patients with hypertension: comparison of assay methods and antigens
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“Among patients with hypertension, it appears that CMV infection is linked to T cell-driven inflammation via an emerging concept termed immune aging or immunosenescence, in which the functions of immune cells or immune organs are altered with increasing age [7, 8].”
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The Ambiguity in Immunology
Barnaba, V., Paroli, M., & Piconese, S. (2012) · Frontiers in Immunology · doi:10.3389/fimmu.2012.00018 · Cited by 15
TCR Down-Regulation Controls T Cell Homeostasis
Boding, L., Bonefeld, C. M., Nielsen, B. L., Lauritsen, J. P. H., von Essen, M. R., Hansen, A. K., Larsen, J. M., Nielsen, M. M., Ødum, N., & Geisler, C. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0901539 · Cited by 14
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“Nevertheless, both require lifelong T cell-mediated immunity for their control within latently infected hosts [25,26].”
Background
Anti-cytomegalovirus antibody levels stratify human immune profiles across the lifespan
Watanabe, M., Davidson, L., Smith, P., Castellucio, P. F., Jergović, M., Uhrlaub, J. L., Smithey, M. J., Fantry, L. E., Dechambre, B., Wilson, R. C., et al. (2024) · GeroScience · doi:10.1007/s11357-024-01124-0 · Cited by 15
“…to live long lives with hCMV and no apparent virus-related pathology making hCMV acquisition a part of the normative aging process in most humans [6]. hCMV is one of the master evaders of the immune system [7], and is known to modulate many parameters of systemic immunity more than any other…”
Senescence-associated T cells in immunosenescence and diseases
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Sahmoudi, K., Allam, A. E., Fakihi, S. E., Tahoune, H., Sadak, A., Hafidi, N. E., Bourkadi, J. E., Aouad, R. E., & Seghrouchni, F. (2020) · Journal of Immunoassay and Immunochemistry · doi:10.1080/15321819.2020.1728543 · Cited by 12
Age-related changes in spleen of Dark Agouti rats immunized for experimental autoimmune encephalomyelitis
Djikić, J., Nacka-Aleksić, M., Pilipović, I., Kosec, D. J., Arsenović-Ranin, N., Stojić-Vukanić, Z., Dimitrijević, M., & Leposavić, G. (2014) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2014.12.014 · Cited by 13
Intrinsic and Extrinsic Thymic Adrenergic Networks: Sex Steroid-Dependent Plasticity
Leposavić, G., & Pilipović, I. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00013 · Cited by 13
Systemic antitumor effect by regional hyperthermia combined with low-dose chemotherapy and immunologic correlates in an adolescent patient with rhabdomyosarcoma – a case report
Issels, R. D., Lindner, L. H., von Bergwelt‐Baildon, M., Lang, P., Rischpler, C., Diem, H., Mosetter, B., Eckl, J., Schendel, D. J., Salat, C., et al. (2020) · International Journal of Hyperthermia · doi:10.1080/02656736.2019.1709666 · Cited by 13
“Indeed, an unlimited consumption of naive T cells can lead to loss of immune control, a situation that is observed in persistent infection [30].”
Background
The Role of Senescence, its Therapeutic Relevance and Clinical Implications in the Tumor Microenvironment
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Limited restoration of T cell subset distribution and immune function in older people living with HIV-1 receiving HAART
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“This, in turn, diminishes the immune system’s ability to recognize neoantigens and increases the risk of age-related diseases [67].”
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Orai, STIM, and PMCA contribute to reduced calcium signal generation in CD8+ T cells of elderly mice
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“A growing body of evidence has linked the chronic infection, especially cytomegalovirus (CMV) (Nikolich-Zugich, 2008; Brunner et al , 2011; Pawelec & Derhovanessian, 2011; Fulop et al , 2013), to the cause of immunoaging in the organismal level.”
Influential
Maintenance of CMV-specific CD8+ T cell responses and the relationship of IL-27 to IFN-γ levels with aging
Shin, M. S., Lee, J. S., Lee, N., Lee, W., Kim, S. H., & Kang, I. (2012) · Cytokine · doi:10.1016/j.cyto.2012.11.024 · Cited by 12
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Deletional and regulatory mechanisms coalesce to drive transplantation tolerance through mixed chimerism
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Transcriptional insights into the CD8+ T cell response in mono-HIV and HCV infection
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An altered relationship of influenza vaccine-specific IgG responses with T cell immunity occurs with aging in humans
Kang, K. S., Lee, N., Shin, M. S., Kim, S. D., Yu, Y., Mohanty, S., Belshe, R. B., Montgomery, R. R., Shaw, A. C., & Kang, I. (2013) · Clinical Immunology · doi:10.1016/j.clim.2013.02.022 · Cited by 10
Cord blood as a source of non-senescent lymphocytes for tumor immunotherapy
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Aging of the Immune System Across Different Species
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Self-citation
Early life thymectomy induces arterial dysfunction in mice
Buckley, D. J., Sharma, S., Joseph, B., Fayyaz, A. H., Canizales, A., Terrebonne, K. J., & Trott, D. W. (2023) · GeroScience · doi:10.1007/s11357-023-00853-y · Cited by 9
“It is well described that age associated thymic involution results in a decreased T cell repertoire and a forced shift from a naïve to a memory T cell phenotype [4, 8, 51–53].”
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Immunosenescence and organoids: pathophysiology and therapeutic opportunities
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“Several discoveries have demonstrated that persistent antigen stimulation is associated with immunose-nescence [138].”
Psychoneuromicrobiology: Cytomegalovirus Infection as a Putative Link Between Stress, Aging, and Immunity
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CD8+ T-cell senescence: no role for mTOR
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Thymic function is a major determinant of onset of antibody-mediated rejection in heart transplantation
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Presence of Senescent and Memory CD8+ Leukocytes as Immunocenescence Markers in Skin Lesions of Elderly Leprosy Patients
da Silva, P. H. L., de Castro, K. K. G., Mendes, M. A., Leal-Calvo, T., Leal, J. M. P., Nery, J. A. D. C., Sarno, E. N., Lourenço, R. A., Moraes, M. O., Lara, F. A., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.647385 · Cited by 9
Alpha beta-crystallin expression and presentation following infection with murine gammaherpesvirus 68
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“Due to the proposed immune dysregulation associated with gammaherpesvirus latency and reactivation over the life of the host [62,63], and due to the wide variation of EBV viral burden between individuals [63–67], mechanisms mediating a virusexacerbated autoimmune response cannot necessarily be assumed to be wholly aut…”
Background
Ovarian hormone level alterations during rat post-reproductive life-span influence CD8 + T-cell homeostasis
Arsenović-Ranin, N., Kosec, D. J., Nacka-Aleksić, M., Pilipović, I., Stojić-Vukanić, Z., Djikić, J., Bufan, B., & Leposavić, G. (2015) · Experimental Biology and Medicine · doi:10.1177/1535370215570817 · Cited by 9
“This cause age-related narrowing of T-cell repertoire diversity in the periphery, and consequently diminishes the efficacious defense against infection with new or re-emerging pathogens with advanced ages.(1,2,6) The age-related decline in the number of naı̈ve T cells is partially compensated by their homeostatic expa…”
Background

Authors: Nikolich-Žugich, J.
Venue: Nature reviews. Immunology
Publisher: Springer Science and Business Media LLC
Published: 2008-07
Volume: 8
Issue: 7
Pages: 512-522
ISSN: 1474-1733 (ISSN-L)
1474-1741
DOI: 10.1038/nri2318
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: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
www.springer.com/tdm (tdm)
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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Ageing and life-long maintenance of T-cell subsets in the face of latent persistent infections.

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