Quiescence and functional reprogramming of Epstein–Barr virus (EBV)-specific CD8+ T cells during persistent infection
Open accessAbstract
After acute infection Epstein-Barr virus (EBV)-specific memory CD8+ T cells exit cell cycle, and a proportion of these antigen-experienced cells re-express CD45RA (CD45 which predominantly express exon A). However, the signals involved are not known. We investigated the roles of interleukin 15 (IL-15) and interferon-alpha/beta (IFN-I) in these processes, since these mediators have a crucial but undefined role in the maintenance of CD8+ T-cell memory. We show that IFN-I (but not IL-15) allows activated EBV-specific CD8+ T cells to leave cell cycle without entering apoptosis. This was associated with up-regulation of the cyclin inhibitor p27, but not of CD45RA. In contrast, IL-15 (but not IFN-I) induced "homeostatic" proliferation and CD45RA re-expression by these cells in vitro. Different signals, therefore, induce quiescence and CD45RA re-expression in activated EBV-specific CD8+ T cells. After T-cell receptor (TCR) activation freshly isolated CD45RA+ antigen-experienced CD8+ T cells show poor proliferative activity but are highly cytotoxic and secrete IFN-gamma efficiently. This suggests functional reprogramming toward effector function but away from proliferation. The induction of quiescence and the generation of proliferation-independent effector CD8+ T cells that re-express CD45RA may minimize the impact of replicative senescence in virus-specific populations that would otherwise occur during decades of persistent infection.
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Senescent T cells within both CD4+ and CD8+ subsets express high levels of intracellular granules containing perforin and granzyme B and can mediate spontaneous antigen-specific cytotoxicity against infected target cells.
“Senescent T cells within both CD4 + and CD8 + subsets express high levels of intracellular granules containing the cytotoxic proteins perforin and granzyme B and can mediate spontaneous antigen-specific cytotoxicity against infected target cells [47-49].”
From Senescence of T Lymphocytes: Implications for Enhancing Human Immunity (2016) · cites this paper as [48]
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- Authors
- Dunne, P. J.
- Affiliations
- The Royal Free Hospital (GB)
- Corresponding author
- Dunne, P. J.
- ORCID
- Dunne, P. J.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2005-07-15
- Volume
- 106
- Issue
- 2
- Pages
- 558-565
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2147260548
- Cited by
- 53
- References
- 49
- Citations by year
- 2026: 3 · 2025: 2 · 2023: 2 · 2022: 2 · 2021: 1 · 2020: 2 · 2019: 3 · 2018: 1 · 2017: 1 · 2016: 2 · 2014: 1 · 2013: 1 · 2012: 2
- FWCI
- 2.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Oncology › Viral-associated cancers and disorders
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- Epstein-Barr virus, CD8+ T cells, T cell quiescence, IL-15, type I interferon, p27, homeostatic proliferation, replicative senescence, effector T cells, viral persistence, T cell receptor stimulation, interferon-gamma, cytotoxicity
- MeSH terms
- Cell Cycle, Cytotoxicity, Immunologic, Herpesvirus 4, Human, Humans, Immunologic Memory, Interferon Type I, Lymphocyte Activation, Recombinant Proteins, Case-Control Studies, Leukocyte Common Antigens, CD8-Positive T-Lymphocytes, Interleukin-15, Epstein-Barr Virus Infections, In Vitro Techniques
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