Expansion of cytotoxic CD8 + CD28 − T cells in healthy ageing people, including centenarians
Abstract
Ageing is associated with complex remodelling in the phenotypic and functional profiles of T lymphocytes. We investigated whether expression of CD28 antigen on T cells is conserved throughout adulthood and ageing in humans. For this purpose we analysed T cells obtained from peripheral blood of 102 healthy people of ages ranging from 20 to 105 years. We found an age‐related increase of CD28 − T cells in percentage and absolute number, predominantly among CD8 + T cells. CD28 − T cells from aged donors analysed by flow cytometry appeared as resting cells (not expressing CD25, CD38, CD69, CD71, DR), bearing markers of cytotoxic activity (CD11b and CD57) and with a phenotype compatible with ‘memory’ cells (up‐regulated CD2 and CD11a; CD62L absent). At the functional level, freshly isolated purified CD28 − CD8 + T cells showed high anti‐CD3 redirected cytotoxic activity against Fc‐bearing P815 cells. The same activity tested on freshly isolated bulk T lymphocytes was significantly augmented with age. We found a positive correlation between age, number of CD8 + CD28 − T cells and anti‐CD3 redirected cytotoxicity by freshly isolated T cells. These data suggest that an activation of unknown nature within the cytotoxic arm of the immune system occurs with age. We speculate that these cytotoxic T lymphocytes (CTL) in vivo may constitute armed effector cells for immediate killing of targets bearing peptides from pathogens of intracellular origin.
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Expansion of the memory population of highly cytotoxic CD8+CD28− T cells is an established hallmark of adaptive immune ageing.
“An established hallmark of adaptive immune ageing is the expansion of the memory population of highly cytotoxic CD8+CD28− T cells114”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [114]
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- Authors
- FAGNONI, F. F., VESCOVINI, R., MAZZOLA, M., BOLOGNA, G., NIGRO, E., LAVAGETTO, G., FRANCESCHI, C., PASSERI, M., & SANSONI, P.
- Affiliations
- University of Parma (IT)
- University of Modena and Reggio Emilia (IT)
- Corresponding author
- SANSONI, P.
- ORCID
- FRANCESCHI, C.
- Venue
- Immunology
- Publisher
- Wiley
- Published
- 1996-08
- Volume
- 88
- Issue
- 4
- Pages
- 501-507
- ISSN
- 0019-2805 (ISSN-L)
- 1365-2567
- OpenAlex
- W2030414136
- Cited by
- 362
- References
- 36
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 13 · 2023: 12 · 2022: 15 · 2021: 13 · 2020: 14 · 2019: 13 · 2018: 15 · 2017: 23 · 2016: 12 · 2015: 8 · 2014: 13 · 2013: 9 · 2012: 5
- FWCI
- 4.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Centre National de la Recherche Scientifique
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- CD28-negative T cells, CD8+ T cells, cytotoxic T lymphocytes, aging, centenarians, T cell activation, cytotoxicity, T cell memory phenotype, CD11b, CD57, age-related immune changes
- MeSH terms
- Adult, Aged, Aged, 80 and over, Aging, Cell Separation, Cytotoxicity, Immunologic, Flow Cytometry, Humans, Middle Aged, CD3 Complex, CD28 Antigens, CD8-Positive T-Lymphocytes, Lymphocyte Count
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