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Origin and differentiation of human memory CD8 T cells after vaccination
Open accessAbstract
The differentiation of human memory CD8 T cells is not well understood. Here we address this issue using the live yellow fever virus (YFV) vaccine, which induces long-term immunity in humans. We used in vivo deuterium labelling to mark CD8 T cells that proliferated in response to the virus and then assessed cellular turnover and longevity by quantifying deuterium dilution kinetics in YFV-specific CD8 T cells using mass spectrometry. This longitudinal analysis showed that the memory pool originates from CD8 T cells that divided extensively during the first two weeks after infection and is maintained by quiescent cells that divide less than once every year (doubling time of over 450 days). Although these long-lived YFV-specific memory CD8 T cells did not express effector molecules, their epigenetic landscape resembled that of effector CD8 T cells. This open chromatin profile at effector genes was maintained in memory CD8 T cells isolated even a decade after vaccination, indicating that these cells retain an epigenetic fingerprint of their effector history and remain poised to respond rapidly upon re-exposure to the pathogen.
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“the generation of robust T cell responses by mRNA vaccines may have implications for long-term protective immunity, as memory CD4+ and CD8+ T cells can be exceptionally durable in other vaccine settings (Akondy et al., 2017; Hammarlund et al., 2003).”
From Rapid induction of antigen-specific CD4+ T cells is associated with coordinated humoral and cellular immunity to SARS-CoV-2 mRNA vaccination (2021) · cites this paper as Akondy et al., 2017
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Metadata
- Authors
- Akondy, R. S., Fitch, M., Edupuganti, S., Yang, S., Kissick, H. T., Li, K. W., Youngblood, B. A., Abdelsamed, H. A., McGuire, D. J., Cohen, K. W., Alexe, G., Nagar, S., McCausland, M. M., Gupta, S., Tata, P., Haining, W. N., McElrath, M. J., Zhang, D., Hu, B., Greenleaf, W. J., Goronzy, J. J., Mulligan, M. J., Hellerstein, M., & Ahmed, R.
- Affiliations
- Emory University (US)
- University of California, Berkeley (US)
- Central South University (CN)
- KineMed (United States) (US)
- St. Jude Children's Research Hospital (US)
- Fred Hutch Cancer Center (US)
- Broad Institute (US)
- Strand Life Sciences (India) (IN)
- Stanford Medicine (US)
- Corresponding author
- Hellerstein, Marc
- Ahmed, Rafi
- ORCID
- Venue
- Nature
- Published
- 2017-12-13
- Volume
- 552
- Issue
- 7685
- Pages
- 362-367
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC6037316
- OpenAlex
- W2772063315
- Cited by
- 517
- References
- 32
- Citations by year
- 2026: 36 · 2025: 49 · 2024: 47 · 2023: 57 · 2022: 72 · 2021: 81 · 2020: 71 · 2019: 55 · 2018: 47 · 2017: 2
- FWCI
- 21.74
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institutes of Health (R01-AI43866-07)
- National Institute of Allergy and Infectious Diseases (R01AI043866, R01AI129191, UM1AI068618, UM1AI069481, U19AI057266)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (T32AR050942)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- memory CD8+ T cells, yellow fever vaccine, T cell differentiation, T cell quiescence, cell turnover, deuterium labeling, epigenetic memory, open chromatin, DNA methylation, effector T cells, naive T cells, T cell proliferation
- MeSH terms
- Animals, Cell Differentiation, Chromatin, Deuterium, Half-Life, Humans, Immunologic Memory, Radioisotope Dilution Technique, Transcription, Genetic, Yellow Fever, Yellow fever virus, CD8-Positive T-Lymphocytes, Lymphocyte Count, DNA Methylation, Gene Expression Profiling, Yellow Fever Vaccine, Epigenesis, Genetic, Cell Proliferation, Mice
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