The Size and Phenotype of Virus-Specific T Cell Populations Is Determined by Repetitive Antigenic Stimulation and Environmental Cytokines
Abstract
Based on the expression of the TNFR SFP CD27, two Ag-primed CD8+ T cell subsets can be discerned in the circulation of healthy individuals: CD27+ T cells that produce a variety of cytokines but do not display immediate cytolytic activity; and cytotoxic CD27− T cells, which secrete only IFN-γ and TNF-α. The mechanism that controls the generation of these different phenotypes is unknown. We show that CMV reactivation not only increases the number of virus-specific T cells but also induces their transition from a CD27+ to a CD27− phenotype. In support of a relation between pool size and phenotype in a cohort of latently infected individuals, the number of Ag-specific CD27− CD8+ T cells was found to be linearly related to the total number of CMV-specific CD8+ T cells. In vitro studies revealed that the acquisition of the CD27− phenotype on CMV-specific T cells depended on the interaction of CD27 with its cellular ligand, CD70. Expression of CD70 was proportional to the amount of antigenic stimulation and blocked by the CD4+ T cell-derived cytokine IL-21. Thus, induction of CD70, which may vary in distinct viral infections, appears to be a key factor in determining the size and phenotype of the CMV-specific T cell population in latently infected individuals.
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CMV reactivation causes an expansion of TEMRA cells, compared to other persistent infections that periodically reactivate (e.g., EBV).
“compared to other persistent infections that periodically reactivate (e.g., EBV) it is CMV reactivation that causes an expansion of these cells (Cantisan et al. 2009; Fulop et al. 2013; Gamadia et al. 2004).”
From Is immunosenescence influenced by our lifetime “dose” of exercise? (2016) · cites this paper as Gamadia et al. 2004
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- Authors
- Gamadia, L. E., van Leeuwen, E. M. M., Remmerswaal, E. B. M., Yong, S.-L., Surachno, S., Wertheim-van Dillen, P. M. E., ten Berge, I. J. M., & van Lier, R. A. W.
- Affiliations
- University of Amsterdam (NL)
- Renal Transplant Unit, Department of Internal Medicine, University of Amsterdam , Amsterdam ,
- Laboratory for Experimental Immunology, University of Amsterdam , Amsterdam ,
- Department of Virology, University of Amsterdam , Amsterdam ,
- Corresponding author
- Surachno, Sugianto
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-05
- Volume
- 172
- Issue
- 10
- Pages
- 6107-6114
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2099775781
- Cited by
- 122
- References
- 54
- Citations by year
- 2024: 1 · 2022: 2 · 2021: 2 · 2020: 3 · 2019: 10 · 2018: 1 · 2017: 8 · 2016: 10 · 2015: 9 · 2014: 6 · 2013: 4 · 2012: 6
- FWCI
- 4.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- CD27, CD70, CD8+ cytotoxic T lymphocytes, virus-specific T cells, cytomegalovirus reactivation, T cell phenotype, antigen stimulation, IL-21, TNF receptor superfamily, interferon-gamma, TNF-α
- MeSH terms
- Antigens, Viral, Cells, Cultured, Cytomegalovirus, Cytotoxicity, Immunologic, Dose-Response Relationship, Immunologic, Humans, Ligands, Longitudinal Studies, Lymphocyte Activation, Membrane Proteins, Phosphoproteins, Viral Matrix Proteins, Antigens, CD, Immunophenotyping, T-Lymphocyte Subsets, Cytokines, Virus Latency, Tumor Necrosis Factor Receptor Superfamily, Member 7, CD8-Positive T-Lymphocytes, Lymphocyte Count, Epitopes, T-Lymphocyte, CD27 Ligand
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