| Literature DB >> 29236685 |
Rama S Akondy1,2, Mark Fitch3, Srilatha Edupuganti4, Shu Yang1,2, Haydn T Kissick5, Kelvin W Li6, Ben A Youngblood1,2,7, Hossam A Abdelsamed7, Donald J McGuire1, Kristen W Cohen8, Gabriela Alexe9,10, Shashi Nagar4, Megan M McCausland1,2, Satish Gupta11, Pramila Tata11, W Nicholas Haining9,10, M Juliana McElrath8, David Zhang12, Bin Hu12, William J Greenleaf13, Jorg J Goronzy12, Mark J Mulligan1,4, Marc Hellerstein3,6, Rafi Ahmed1,2.
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.Entities:
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Year: 2017 PMID： 29236685 PMCID： PMC6037316 DOI： 10.1038/nature24633
Source DB: PubMed Journal: Nature ISSN： 0028-0836 Impact factor: 69.504