Cytometry by time-of-flight shows combinatorial cytokine expression and virus-specific cell niches within a continuum of CD8+ T cell phenotypes
Open accessAbstract
Cytotoxic CD8(+) T lymphocytes directly kill infected or aberrant cells and secrete proinflammatory cytokines. By using metal-labeled probes and mass spectrometric analysis (cytometry by time-of-flight, or CyTOF) of human CD8(+) T cells, we analyzed the expression of many more proteins than previously possible with fluorescent labels, including surface markers, cytokines, and antigen specificity with modified peptide-MHC tetramers. With 3-dimensional principal component analysis (3D-PCA) to display phenotypic diversity, we observed a relatively uniform pattern of variation in all subjects tested, highlighting the interrelatedness of previously described subsets and the continuous nature of CD8(+) T cell differentiation. These data also showed much greater complexity in the CD8(+) T cell compartment than previously appreciated, including a nearly combinatorial pattern of cytokine expression, with distinct niches occupied by virus-specific cells. This large degree of functional diversity even between cells with the same specificity gives CD8(+) T cells a remarkable degree of flexibility in responding to pathogens.
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TEMRA T cells are mostly specific for latent viruses such as CMV and EBV, suggesting that nature and chronicity of viral stimulation rather than age drives their functional phenotype.
“As discussed above, these cells are mostly specific for latent viruses, such as CMV and EBV (Newell et al., 2012), suggesting that the nature and chronicity of viral stimulation rather than age drives their functional phenotype”
From Successful and Maladaptive T Cell Aging (2017) · cites this paper as Newell et al., 2012
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- Authors
- Newell, E. W., Sigal, N., Bendall, S. C., Nolan, G. P., & Davis, M. M.
- Affiliations
- Stanford Medicine (US)
- Stanford University (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Davis, Mark M.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2012-01
- Volume
- 36
- Issue
- 1
- Pages
- 142-152
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC3752833
- OpenAlex
- W2095085751
- Cited by
- 555
- References
- 48
- Citations by year
- 2026: 6 · 2025: 14 · 2024: 11 · 2023: 16 · 2022: 16 · 2021: 32 · 2020: 35 · 2019: 45 · 2018: 46 · 2017: 61 · 2016: 61 · 2015: 66 · 2014: 63 · 2013: 52 · 2012: 29
- FWCI
- 29.40
- Type
- journal article
- Language
- en
- Update notices
- erratum (2013-01-24)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute of Allergy and Infectious Diseases (U19AI090019, U19AI057229)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- CD8+ T cells, cytokine expression, virus-specific T cells, T cell differentiation, T cell subsets, peptide-MHC tetramers
- MeSH terms
- Antigens, Viral, Tumor, Flow Cytometry, Humans, Phenotype, Mass Spectrometry, Cytokines, CD8-Positive T-Lymphocytes, Principal Component Analysis
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