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

Effros, Rita B.; Boucher, Nathalie; Porter, Verna; Zhu, Xiaoming; Spaulding, Carolyn; Walford, Roy L.; Kronenberg, Mitchell; Cohen, Daniel; Schächter, François

doi:10.1016/0531-5565(94)90073-6

Cited by 377T-cell and B-cell ImmunologyTelomeres, Telomerase, and SenescenceGenetics, Aging, and Longevity in Model Organisms

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

Effros, Rita B., Boucher, Nathalie, Porter, Verna, Zhu, Xiaoming, Spaulding, Carolyn, Walford, Roy L., Kronenberg, Mitchell, Cohen, Daniel +1 more·1994·Experimental Gerontology

DOI 10.1016/0531-5565(94)90073-6

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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.
“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]
The loss of CD28 occurs following cell proliferation, according to the observation that CD28− T cells have shorter telomeres than CD28+ cells.
“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]
Late-stage memory senescent T-cells may also acquire new functions, such as suppressive activity, as demonstrated in vitro.
“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]
CD28 seems a good biomarker of immunosenescence, as suggested by findings that late-differentiated CD8+/CD28− T cells tend to accumulate particularly in older people, frail or affected by age-related diseases.
“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]
Senescent T cells are producers of pro-inflammatory cytokines.
“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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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.
ORCID: Effros, Rita B.
Boucher, Nathalie
Zhu, Xiaoming
Kronenberg, Mitchell
Cohen, Daniel
Venue: Experimental Gerontology
Publisher: Elsevier BV
Published: 1994-11
Volume: 29
Issue: 6
Pages: 601-609
ISSN: 0531-5565 (ISSN-L)
DOI: 10.1016/0531-5565(94)90073-6
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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
Health Sciences › Medicine › Physiology › 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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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

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