Reduced naïve CD 8 + T ‐cell priming efficacy in elderly adults
Open accessAbstract
Aging is associated with impaired vaccine efficacy and increased susceptibility to infectious and malignant diseases. CD8(+) T-cells are key players in the immune response against pathogens and tumors. In aged mice, the dwindling naïve CD8(+) T-cell compartment is thought to compromise the induction of de novo immune responses, but no experimental evidence is yet available in humans. Here, we used an original in vitro assay based on an accelerated dendritic cell coculture system in unfractioned peripheral blood mononuclear cells to examine CD8(+) T-cell priming efficacy in human volunteers. Using this approach, we report that old individuals consistently mount quantitatively and qualitatively impaired de novo CD8(+) T-cell responses specific for a model antigen. Reduced CD8(+) T-cell priming capacity in vitro was further associated with poor primary immune responsiveness in vivo. This immune deficit likely arises as a consequence of intrinsic cellular defects and a reduction in the size of the naïve CD8(+) T-cell pool. Collectively, these findings provide new insights into the cellular immune insufficiencies that accompany human aging.
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The abundance of naive T cells declines substantially with age.
“it is well characterized that the abundance of naive T cells declines substantially with age (Briceño et al., 2016; Qi et al., 2014; Wertheimer et al., 2014).”
From Adaptive immunity to SARS-CoV-2 and COVID-19 (2021) · cites this paper as Briceño et al., 2016
In older individuals, clonal expansion of Mart1-specific T cells was reduced, and these cells failed to differentiate into T-bet-expressing effector T cells.
“In older individuals, clonal expansion of Mart1-specific T cells was reduced, and importantly, these cells failed to differentiate into T-bet-expressing effector T cells.”
From Successful and Maladaptive T Cell Aging (2017) · cites this paper as Briceño et al., 2016
In vitro results on Mart1-specific T cells correlated with in vivo primary responses after tick-borne encephalitis virus vaccination, supporting in vivo relevance.
“Most interestingly, these in vitro results correlated with in vivo primary responses after vaccination with the tick-born encephalitis virus, supporting the in vivo relevance of these in vitro findings”
From Successful and Maladaptive T Cell Aging (2017) · cites this paper as Briceño et al., 2016
Naïve T cells from old people show altered TCR signaling and TCR-induced ERK phosphorylation, resulting in blunted activation.
“Altered TCR signaling and TCR-induced ERK phosphorylation, resulting in blunted activation, have been reported in CD4+ and CD8+ naïve T cells from old people [81, 82].”
From Aging of the immune system: Focus on inflammation and vaccination (2016) · cites this paper as [82]
In an in vitro T-cell priming model, CD8+ T cells from elderly individuals consistently mounted impaired responses specific to the model neoantigen Melan-A/MART-1.
“Using an in vitro model of T-cell priming, it was indeed shown that CD8+ T cells from elderly individuals consistently mounted impaired responses specific to a model neoantigen, such as Melan-A/MART-1 [82].”
From Aging of the immune system: Focus on inflammation and vaccination (2016) · cites this paper as [82]
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- Authors
- Briceño, O., Lissina, A., Wanke, K., Afonso, G., Braun, A., Ragon, K., Miquel, T., Gostick, E., Papagno, L., Stiasny, K., Price, D. A., Mallone, R., Sauce, D., Karrer, U., & Appay, V.
- Affiliations
- Inserm (FR)
- University Hospital Zurich (CH)
- Centre National de la Recherche Scientifique (FR)
- Centre d'Immunologie et des Maladies Infectieuses (CIMI‐Paris) Sorbonne Universités, UPMC Univ Paris 06, DHU FAST CR7 F‐75013 Paris France
- Institute of Infection and Immunity Cardiff University School of Medicine Cardiff Wales UK
- Medical University of Vienna (AT)
- Cardiff University (GB)
- Corresponding author
- Appay, Victor
- ORCID
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2015-10-15
- Volume
- 15
- Issue
- 1
- Pages
- 14-21
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- PMC
- PMC4717282
- OpenAlex
- W1930328534
- Cited by
- 151
- References
- 44
- Citations by year
- 2026: 11 · 2025: 12 · 2024: 17 · 2023: 13 · 2022: 22 · 2021: 25 · 2020: 18 · 2019: 6 · 2018: 12 · 2017: 7 · 2016: 8
- FWCI
- 4.44
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Aging Cell (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Bristol Research (University of Bristol) (publishedVersion, cc-by)
- ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
- HAL (submittedVersion, cc-by)
- HAL (submittedVersion)
- Explore Bristol Research (submittedVersion, cc-by)
- Funders
- Swiss National Science Foundation (PP0033‐110737)
- 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 › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- CD8+ T cells, naive T cell priming, immunosenescence, aging, vaccine efficacy, older adults
- MeSH terms
- Adult, Aged, Aged, 80 and over, Aging, Dendritic Cells, Female, Flow Cytometry, Humans, Leukocytes, Mononuclear, Lymphocyte Activation, Male, Middle Aged, CD8-Positive T-Lymphocytes, Young Adult
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