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Cited by 90T-cell and B-cell ImmunologyImmunotherapy and Immune ResponsesCytomegalovirus and herpesvirus research

Differential costimulation through CD137 (4–1BB) restores proliferation of human virus-specific “effector memory” (CD28− CD45RAHI) CD8+ T cells

Waller, Edward C. P., McKinney, Nicola, Hicks, Ray, Carmichael, Andrew J., Sissons, J. G. Patrick, Wills, Mark R.·2007·Blood
DOI 10.1182/blood-2007-07-104604
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Abstract

In healthy carriers of human cytomegalovirus (HCMV), the virus-specific memory CD8+ T-cell population is often dominated by CD28− CD45RAhi cells that exhibit direct ex vivo cytotoxicity but whose capacity for proliferation and generation of further memory cells has been questioned. We show that when highly purified CD28− CD45RAhi CD8+ T cells are stimulated with viral peptide presented by autologous monocytes, the virus-specific T cells show early up-regulation of CD137 (4–1BB) and CD278 (ICOS), re-express CD28, and proliferate with similarly high cloning efficiency in limiting dilution analysis as CD28+ CD45ROhi cells or CD28− CD45ROhi cells. Using peptide-pulsed autologous fibroblasts transfected with individual costimulatory ligands as antigen presenting cells, we showed CD137L to be a key costimulatory ligand for proliferation of CD28− CD45RAhi CD8+ T cells and not CD80, CD86, or CD275 (ICOSL). Therefore, CD28− CD45RAhi CD8+ T cells were not terminally differentiated but required a specific costimulatory signal for proliferation.

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  • Unlike senescent fibroblasts, T cells with characteristics of senescence are prone to apoptosis in vitro.

    “Unlike senescent fibroblasts however, T cells that have characteristics of senescence are prone to apoptosis in vitro [23, 28] although they may be induced to persist by appropriate signals such as growth factors in vivo [32].”

    From Senescence of T Lymphocytes: Implications for Enhancing Human Immunity (2016) · cites this paper as [32]

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Authors
Waller, E. C. P., McKinney, N., Hicks, R., Carmichael, A. J., Sissons, J. G. P., & Wills, M. R.
Affiliations
University of Cambridge (GB)
ORCID
Wills, Mark R.
Venue
Blood
Publisher
American Society of Hematology
Published
2007-12-15
Volume
110
Issue
13
Pages
4360-4366
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
DOI
10.1182/blood-2007-07-104604
OpenAlex
W2021512211
Cited by
90
References
41
Citations by year
2026: 2 · 2025: 2 · 2024: 2 · 2023: 5 · 2022: 2 · 2020: 1 · 2019: 3 · 2018: 8 · 2017: 3 · 2016: 3 · 2015: 3 · 2014: 6 · 2013: 5 · 2012: 3
FWCI
3.57
Type
journal article
Language
en
Open access
closed
Locations
  • Blood (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
Keywords
CD137 (4-1BB), CD28, CD8+ T cells, effector memory T cells, T cell proliferation, costimulation, human cytomegalovirus, virus-specific T cells, CD137L, ICOSL, CD80, CD86, T cell differentiation
MeSH terms
Antigens, Differentiation, T-Lymphocyte, Antigens, Viral, Cells, Cultured, Cytomegalovirus, Fibroblasts, Humans, Immunologic Memory, Signal Transduction, Up-Regulation, Leukocyte Common Antigens, CD28 Antigens, CD8-Positive T-Lymphocytes, Cell Proliferation, Tumor Necrosis Factor Receptor Superfamily, Member 9, Inducible T-Cell Co-Stimulator Protein

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