Differentiation of human CD8 T cells: implications for in vivo persistence of CD8+ CD28− cytotoxic effector clones

Posnett, David N.; Edinger, James W.; Manavalan, J. Sanil; Irwin, Craig; Marodon, Gilles

doi:10.1093/intimm/11.2.229

Cited by 202T-cell and B-cell ImmunologyImmunotherapy and Immune ResponsesHIV Research and Treatment

Differentiation of human CD8 T cells: implications for in vivo persistence of CD8+ CD28− cytotoxic effector clones

Posnett, David N., Edinger, James W., Manavalan, J. Sanil, Irwin, Craig, Marodon, Gilles·1999·International Immunology

DOI 10.1093/intimm/11.2.229

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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 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 [42]
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 [42]
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 [42]
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 [42]
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 [42]

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CD28- T lymphocytes. Antigenic and functional properties
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Differentiation of Human CD8+ T Cells from a Memory to Memory/Effector Phenotype
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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
DOI: 10.1093/intimm/11.2.229
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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Differentiation of human CD8 T cells: implications for in vivo persistence of CD8+ CD28− cytotoxic effector clones

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