The DOI matches its Crossref record; 57 of the 58 references it cites were found in a registry or an index.
Differentiation of human CD8 T cells: implications for in vivo persistence of CD8+ CD28− cytotoxic effector clones
Abstract
CD8 T cells contain a distinct subset of CD8+ CD28- cells. These cells are not present at birth and their frequency increases with age. They frequently contain expanded clones using various TCRalphabeta receptors and these clones can represent >50% of all CD8 cells, specially in old subjects or patients with chronic viral infections such as HIV-1. Herein, it is shown that a large fraction of CD8+ CD28- cells expresses intracellular perforin by three-color flow cytometry, in particular when this subset is expanded. Together with their known ability to exert potent re-directed cytotoxicity, this indicates that CD8+ CD28- T cells comprise cytotoxic effector cells. With BrdU labeling, we show that CD8+ CD28- cells derive from CD8+ CD28+ precursors in vitro. In addition, sorted CD8+ CD28+ cells gave rise to a population of CD8+ CD28- cells after allo-stimulation. Moreover, ex vivo CD8+ CD28+ cells contain the majority of CD8 blasts, supporting the notion that they contain the proliferative precursors of CD8+ CD28- cells. CD95 (Fas) expression was lower in CD8+ CD28- cells, and this subset was less prone to spontaneous apoptosis in ex vivo samples and more resistant to activation-induced cell death induced by a superantigen in vitro. Thus, the persistence of expanded clones in vivo in the CD8+ CD28- subset may be explained by antigen-driven differentiation from CD8+ CD28+ memory precursors, with relative resistance to apoptosis as the clones become perforin(+) effector cells.
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“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 [42]
In the citing paper
“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 [42]
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 [42]
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 [42]
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 [42]
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Metadata
- Authors
- Posnett, D. N., Edinger, J. W., Manavalan, J. S., Irwin, C., & Marodon, G.
- Affiliations
- Cornell University (US)
- Corresponding author
- Posnett, David N.
- ORCID
- Marodon, Gilles
- Venue
- International Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 1999-02
- Volume
- 11
- Issue
- 2
- Pages
- 229-241
- ISSN
- 0953-8178 (ISSN-L)
- 1460-2377
- OpenAlex
- W2117623957
- Cited by
- 202
- References
- 58
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2022: 4 · 2021: 4 · 2020: 2 · 2019: 8 · 2018: 3 · 2017: 6 · 2016: 3 · 2015: 2 · 2014: 5 · 2012: 5
- FWCI
- 6.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Drug Abuse
- National Institute of Allergy and Infectious Diseases (AI-22333)
- 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 › Virology › HIV Research and Treatment
- Keywords
- CD8+CD28- T cells, T cell differentiation, cytotoxic effector cells, perforin, apoptosis resistance, Fas/CD95, T cell clonal expansion, HIV-1, chronic viral infection, T cell persistence
- MeSH terms
- Adult, Aged, Aging, Cell Differentiation, Clone Cells, Humans, Membrane Glycoproteins, Middle Aged, T-Lymphocytes, Cytotoxic, T-Lymphocyte Subsets, Receptors, Antigen, T-Cell, alpha-beta, Apoptosis, Superantigens, CD28 Antigens, CD8-Positive T-Lymphocytes, Pore Forming Cytotoxic Proteins, Perforin
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