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Origin and differentiation of human memory CD8 T cells after vaccination

Author

Listed:
  • Rama S. Akondy

    (Emory Vaccine Center, Emory University School of Medicine
    Emory University School of Medicine)

  • Mark Fitch

    (UC Berkeley)

  • Srilatha Edupuganti

    (Emory University School of Medicine)

  • Shu Yang

    (Emory Vaccine Center, Emory University School of Medicine
    Emory University School of Medicine
    Central South University)

  • Haydn T. Kissick

    (Emory University School of Medicine)

  • Kelvin W. Li

    (KineMed Inc.)

  • Ben A. Youngblood

    (Emory Vaccine Center, Emory University School of Medicine
    Emory University School of Medicine
    St.Jude Children’s Research Hospital)

  • Hossam A. Abdelsamed

    (St.Jude Children’s Research Hospital)

  • Donald J. McGuire

    (Emory Vaccine Center, Emory University School of Medicine)

  • Kristen W. Cohen

    (Fred Hutchinson Cancer Research Center)

  • Gabriela Alexe

    (Dana-Farber Cancer Institute, Harvard Medical School
    Broad Institute of MIT and Harvard)

  • Shashi Nagar

    (Emory University School of Medicine)

  • Megan M. McCausland

    (Emory Vaccine Center, Emory University School of Medicine
    Emory University School of Medicine)

  • Satish Gupta

    (Strand Lifesciences)

  • Pramila Tata

    (Strand Lifesciences
    Syngene International)

  • W. Nicholas Haining

    (Dana-Farber Cancer Institute, Harvard Medical School
    Broad Institute of MIT and Harvard)

  • M. Juliana McElrath

    (Fred Hutchinson Cancer Research Center)

  • David Zhang

    (Stanford University School of Medicine)

  • Bin Hu

    (Stanford University School of Medicine)

  • William J. Greenleaf

    (Stanford University School of Medicine)

  • Jorg J. Goronzy

    (Stanford University School of Medicine)

  • Mark J. Mulligan

    (Emory Vaccine Center, Emory University School of Medicine
    Emory University School of Medicine)

  • Marc Hellerstein

    (UC Berkeley
    KineMed Inc.)

  • Rafi Ahmed

    (Emory Vaccine Center, Emory University School of Medicine
    Emory University School of Medicine)

Abstract

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.

Suggested Citation

  • Rama S. Akondy & Mark Fitch & Srilatha Edupuganti & Shu Yang & Haydn T. Kissick & Kelvin W. Li & Ben A. Youngblood & Hossam A. Abdelsamed & Donald J. McGuire & Kristen W. Cohen & Gabriela Alexe & Shas, 2017. "Origin and differentiation of human memory CD8 T cells after vaccination," Nature, Nature, vol. 552(7685), pages 362-367, December.
    • Handle: RePEc:nat:nature:v:552:y:2017:i:7685:d:10.1038_nature24633
    DOI: 10.1038/nature24633
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    Cited by:

    1. Monica Neagu & Carolina Constantin & Mihaela Surcel, 2021. "Testing Antigens, Antibodies, and Immune Cells in COVID-19 as a Public Health Topic—Experience and Outlines," IJERPH, MDPI, vol. 18(24), pages 1-16, December.
    2. Fulvio Lauretani & Marco Salvi & Irene Zucchini & Crescenzo Testa & Chiara Cattabiani & Arianna Arisi & Marcello Maggio, 2023. "Relationship between Vitamin D and Immunity in Older People with COVID-19," IJERPH, MDPI, vol. 20(8), pages 1-19, April.
    3. Joshua S. Woodworth & Vanessa Contreras & Dennis Christensen & Thibaut Naninck & Nidhal Kahlaoui & Anne-Sophie Gallouët & Sébastien Langlois & Emma Burban & Candie Joly & Wesley Gros & Nathalie Dereud, 2024. "MINCLE and TLR9 agonists synergize to induce Th1/Th17 vaccine memory and mucosal recall in mice and non-human primates," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    4. Matthias Reinscheid & Hendrik Luxenburger & Vivien Karl & Anne Graeser & Sebastian Giese & Kevin Ciminski & David B. Reeg & Valerie Oberhardt & Natascha Roehlen & Julia Lang-Meli & Kathrin Heim & Nina, 2022. "COVID-19 mRNA booster vaccine induces transient CD8+ T effector cell responses while conserving the memory pool for subsequent reactivation," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    5. S. Fiorenza & Y. Zheng & J. Purushe & T. J. Bock & J. Sarthy & D. H. Janssens & A. S. Sheih & E. L. Kimble & D. Kirchmeier & T. D. Phi & J. Gauthier & A. V. Hirayama & S. R. Riddell & Q. Wu & R. Gotta, 2024. "Histone marks identify novel transcription factors that parse CAR-T subset-of-origin, clinical potential and expansion," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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