Cited by 169T-cell and B-cell ImmunologyCell death mechanisms and regulationImmune Response and Inflammation

Clonality and longevity of CD4+CD28null T cells are associated with defects in apoptotic pathways

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Vallejo, Abbe N, Schirmer, Michael, Weyand, Cornelia M, Goronzy, Jörg J·2000·The Journal of Immunology

Abstract

CD4+CD28null T cells are oligoclonal lymphocytes rarely found in healthy individuals younger than 40 yr, but are found in high frequencies in elderly individuals and in patients with chronic inflammatory diseases. Contrary to paradigm, they are functionally active and persist over many years. Such clonogenic potential and longevity suggest altered responses to apoptosis-inducing signals. In this study, we show that CD4+CD28null T cells are protected from undergoing activation-induced cell death. Whereas CD28+ T cells underwent Fas-mediated apoptosis upon cross-linking of CD3, CD28null T cells were highly resistant. CD28null T cells were found to progress through the cell cycle, and cells at all stages of the cell cycle were resistant to apoptosis, unlike their CD28+ counterparts. Neither the activation-induced up-regulation of the IL-2R α-chain (CD25) nor the addition of exogenous IL-2 renders them susceptible to Fas-mediated apoptosis. These properties of CD28null T cells were related to high levels of Fas-associated death domain-like IL-1-converting enzyme-like inhibitory protein, an inhibitor of Fas signaling that is normally degraded in T cells following activation in the presence of IL-2. Consistent with previous data showing protection of CD28null cells from spontaneous cell death, the present studies unequivocally show dysregulation of apoptotic pathways in CD4+CD28null T cells that favor their clonal outgrowth and maintenance in vivo.

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Crossref · 10.4049/jimmunol.165.11.6301

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Authors
Vallejo, A. N., Schirmer, M., Weyand, C. M., & Goronzy, J. J.
Affiliations
  • Mayo Clinic (US)
  • Departments of Medicine and Immunology, Mayo Clinic and Foundation , Rochester, MN 55905
Venue
The Journal of Immunology
Published
2000-12-01
Volume
165
Issue
11
Pages
6301-6307
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
OpenAlex
W2127708226
Cited by
169
References
49
Citations by year
2026: 2 · 2025: 1 · 2024: 4 · 2023: 4 · 2022: 6 · 2021: 5 · 2020: 4 · 2019: 7 · 2018: 8 · 2017: 7 · 2016: 10 · 2015: 5 · 2014: 6 · 2013: 10 · 2012: 10
FWCI
2.83
Type
journal article
Language
en
Open access
Locations
  • The Journal of Immunology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Mayo Foundation for Medical Education and Research
  • National Institutes of Health
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR041974, R01 AR 41974, R01AR042527, R01AR42527, R03-AR45830, R03AR045830)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords
CD4+CD28null T cells, CD28, apoptosis resistance, Fas-mediated apoptosis, activation-induced cell death, interleukin-2, CD25, cell cycle progression, T cell clonality, T cell longevity, aging, chronic inflammation
MeSH terms
Adult, Carrier Proteins, Cell Cycle, Cell Line, Cell Survival, Clone Cells, Humans, Immunity, Innate, Ligands, Lymphocyte Activation, Membrane Glycoproteins, Solubility, Receptors, Interleukin-2, Signal Transduction, CD4 Antigens, T-Lymphocyte Subsets, Apoptosis, CD28 Antigens, fas Receptor, Jurkat Cells, Intracellular Signaling Peptides and Proteins, Caspase 8, Fas Ligand Protein, CASP8 and FADD-Like Apoptosis Regulating Protein, Caspase 9, Caspase Inhibitors

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