Heightened self-reactivity associated with selective survival, but not expansion, of naïve virus-specific CD8 + T cells in aged mice

Quinn, Kylie M.; Zaloumis, Sophie G.; Cukalac, Tania; Kan, Wan-Ting; Sng, Xavier Y. X.; Mirams, Michiko; Watson, Katherine A.; McCaw, James M.; Doherty, Peter C.; Thomas, Paul G.; Handel, Andreas; La Gruta, Nicole L.

doi:10.1073/pnas.1525167113

Cited by 47T-cell and B-cell ImmunologyImmunotherapy and Immune Responsesvaccines and immunoinformatics approaches

Heightened self-reactivity associated with selective survival, but not expansion, of naïve virus-specific CD8 + T cells in aged mice

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Quinn, Kylie M., Zaloumis, Sophie G., Cukalac, Tania, Kan, Wan-Ting, Sng, Xavier Y. X., Mirams, Michiko, Watson, Katherine A., McCaw, James M. +4 more·2016·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.1525167113PMC PMC4747731

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Abstract

Significance: Compromised CD8 + T-cell immunity is associated with significant morbidity and mortality in the elderly. Whereas the number of naïve CD8 + T cells declines with age, the drivers of loss and consequences for clonal composition are unclear. We show that aging disproportionately impacts small naïve CD8 + T-cell populations. For one CD8 + T-cell population, loss of diversity was minimally attributable to expansion but rather was associated with diminished cell number and selective retention of cells exhibiting markers of heightened self, but not foreign, recognition. Thus, vaccine formulations for the elderly may benefit from targeting naïve antigen-specific populations with relatively high precursor frequency and self-reactivity, and retention of high-quality T cells may be achieved through repeated low-level T-cell receptor stimulation.

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Some clones selected during homeostatic proliferation may have higher self-affinity and promote autoreactive immunity in the elderly.
“some of these clones selected during homeostatic proliferation may have a higher affinity to self and therefore promote autoreactive immunity in the elderly”
From Successful and Maladaptive T Cell Aging (2017) · cites this paper as Quinn et al., 2016

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Authors: Quinn, K. M., Zaloumis, S. G., Cukalac, T., Kan, W.-T., Sng, X. Y. X., Mirams, M., Watson, K. A., McCaw, J. M., Doherty, P. C., Thomas, P. G., Handel, A., & La Gruta, N. L.
Affiliations: The University of Melbourne (AU)
St. Jude Children's Research Hospital (US)
University of Georgia (US)
Department of Microbiology and Immunology, Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia;
ORCID: Quinn, Kylie M.
Zaloumis, Sophie G.
Sng, Xavier Y. X.
Watson, Katherine A.
McCaw, James M.
Doherty, Peter C.
Thomas, Paul G.
Handel, Andreas
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2016-01-19
Volume: 113
Issue: 5
Pages: 1333-1338
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.1525167113
PMC: PMC4747731
OpenAlex: W2256621953
Cited by: 47
References: 35
Citations by year: 2026: 3 · 2025: 1 · 2023: 2 · 2022: 3 · 2021: 10 · 2020: 8 · 2019: 6 · 2018: 3 · 2017: 8 · 2016: 3
FWCI: 4.03
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.pnas.org/preview_site/misc/userlicense.xhtml (vor, 182 d)
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Monash University Research Portal (Monash University) (submittedVersion, other-oa)
RMIT Research Repository (RMIT University Library) (submittedVersion)
Figshare (submittedVersion)
Funders: Department of Health, Australian Government | National Health and Medical Research Council (1071916)
HHS | National Institutes of Health (117891)
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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
Keywords: immunosenescence, CD8+ T cells, naive T cells, cytotoxic T lymphocytes, autoreactivity, influenza A virus, T cell receptor repertoire, immunodominance hierarchy, CD44, CD5, CD8 coreceptor, clonal expansion, epitope specificity, aged mice
MeSH terms: Animals, Mice, Inbred C57BL, CD8-Positive T-Lymphocytes, Mice

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Heightened self-reactivity associated with selective survival, but not expansion, of naïve virus-specific CD8 + T cells in aged mice

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