The DOI matches its Crossref record; 21 of the 21 references it cites were found in a registry or an index.
Decline in CD28+ T cells in centenarians and in long-term T cell cultures: A possible cause for both in vivo and in vitro immunosenescence
Abstract
The dramatic decline in immune function with age, especially in T cell proliferative activity, has been documented extensively in experimental animal models and in clinical studies of the elderly. A similar proliferative decline is also seen in long-term T lymphocyte cultures used to study in vitro cellular senescence. We have compared the peripheral blood T lymphocytes of centenarians and younger controls for the cell surface expression of CD28, a costimulatory molecule that is required for optimal activation and proliferation following engagement of the T cell receptor. Our analysis shows a significant decrease (p < 0.001) in the percentage of T cells expressing CD28 in the elderly cohort, with values ranging from 44% to 90%, as compared to the mean control value of 91%. The decline in the percentage of CD28+ T cells correlates with a reduction in the CD4/CD8 ratio (r2 = 0.695, p < 0.0001). Concommitantly, experiments using an in vitro T cell culture system showed a progressive loss of CD28 expression with culture "age." The concordance of proliferative decline and loss of CD28 in the centenarians and in the in vitro cultures suggest that a Hayflick phenomenon may operate in vivo leading to immunosenescence.
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“These T cells do not express the co-stimulatory molecule CD28, required for the activation of T cells.”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [41]
In the citing paper
“The loss of CD28 occurs following cell proliferation, according to the observation that the CD28− T cells have shorter telomeres than CD28+ cells.”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [41]
In the citing paper
“Late-stage memory senescent T-cells may also acquire new functions, such as suppressive activity, as demonstrated in vitro.”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [41]
In the citing paper
“CD28 seems a good biomarker of immunosenescence, as further suggested by findings that late-differentiated CD8+/CD28− T cells tend to accumulate particularly in older people, frail or affected by age-related diseases.”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [41]
In the citing paper
“In addition, they are producers of pro-inflammatory cytokines (17, 18, 41–47).”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [41]
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Metadata
- Authors
- Effros, R. B., Boucher, N., Porter, V., Zhu, X., Spaulding, C., Walford, R. L., Kronenberg, M., Cohen, D., & Schächter, F.
- Affiliations
- University of California, Los Angeles (US)
- Fondation Jean Dausset-CEPH (FR)
- Corresponding author
- Effros, Rita B.
- Venue
- Experimental Gerontology
- Publisher
- Elsevier BV
- Published
- 1994-11
- Volume
- 29
- Issue
- 6
- Pages
- 601-609
- ISSN
- 0531-5565 (ISSN-L)
- OpenAlex
- W2037915406
- Cited by
- 377
- References
- 21
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 3 · 2023: 8 · 2022: 6 · 2021: 13 · 2020: 8 · 2019: 17 · 2018: 14 · 2017: 14 · 2016: 11 · 2015: 9 · 2014: 10 · 2013: 16 · 2012: 14
- FWCI
- 3.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Gerontology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Amgen
- National Institutes of Health (5r01ag005309-06)
- National Institute on Aging (AG00427, AG05309, AG-00424)
- 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 › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- immunosenescence, CD28, centenarians, T cell proliferation, cellular senescence, CD4/CD8 ratio, costimulatory molecules
- MeSH terms
- Adult, Aged, Aged, 80 and over, Cells, Cultured, Humans, Middle Aged, T-Lymphocytes, Linear Models, Case-Control Studies, T-Lymphocyte Subsets, Cellular Senescence, CD28 Antigens, Lymphocyte Count
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