Origin and differentiation of human memory CD8 T cells after vaccination

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, Shashi Nagar, Megan M. McCausland, Satish Gupta, Pramila Tata, W. Nicholas Haining, M. Juliana McElrath, David Zhang, Bin Hu, William J. Greenleaf, Jorg J. Goronzy, Mark J. Mulligan, Marc Hellerstein () and Rafi Ahmed ()
Additional contact information
Rama S. Akondy: Emory Vaccine Center, 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
Haydn T. Kissick: Emory University School of Medicine
Kelvin W. Li: KineMed Inc.
Ben A. Youngblood: Emory Vaccine Center, Emory University School of Medicine
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
Shashi Nagar: Emory University School of Medicine
Megan M. McCausland: Emory Vaccine Center, Emory University School of Medicine
Satish Gupta: Strand Lifesciences
Pramila Tata: Strand Lifesciences
W. Nicholas Haining: Dana-Farber Cancer Institute, Harvard Medical School
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
Marc Hellerstein: UC Berkeley
Rafi Ahmed: Emory Vaccine Center, Emory University School of Medicine

Nature, 2017, vol. 552, issue 7685, 362-367

Abstract: 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.

Date: 2017
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DOI: 10.1038/nature24633

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