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Nature. 2017 Dec 21;552(7685):362-367. doi: 10.1038/nature24633. Epub 2017 Dec 13.

Origin and differentiation of human memory CD8 T cells after vaccination.

Author information

1
Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, USA.
2
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA.
3
Department of Nutritional Sciences and Toxicology, UC Berkeley, Berkeley, California, USA.
4
Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, Georgia, USA.
5
Department of Urology, Emory University School of Medicine, Atlanta, Georgia, USA.
6
KineMed Inc., Emeryville California, USA.
7
St.Jude Children's Research Hospital, Memphis, Tennessee, USA.
8
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
9
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
10
Broad Institute of MIT and Harvard, Cambridge, Masschusetts 02142, USA.
11
Strand Lifesciences, Bangalore, India.
12
Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, California, USA.
13
Department of Genetics, Stanford University School of Medicine, Stanford, California, USA.

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.

PMID:
29236685
PMCID:
PMC6037316
DOI:
10.1038/nature24633
[Indexed for MEDLINE]
Free PMC Article

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