Human stem cell-like memory T cells are maintained in a state of dynamic flux
File(s)1-s2.0-S2211124716315959-main.pdf (2.66 MB)
Published version
Author(s)
Type
Journal Article
Abstract
Adaptive immunity requires the generation of memory T cells from naive precursors selected in the thymus. The key intermediaries in this process are stem cell-like memory T (TSCM) cells, multipotent progenitors that can both self-renew and replenish more differentiated subsets of memory T cells. In theory, antigen specificity within the TSCM pool may be imprinted statically as a function of largely dormant cells and/or retained dynamically by more transitory subpopulations. To explore the origins of immunological memory, we measured the turnover of TSCM cells in vivo using stable isotope labeling with heavy water. The data indicate that TSCM cells in both young and elderly subjects are maintained by ongoing proliferation. In line with this finding, TSCM cells displayed limited telomere length erosion coupled with high expression levels of active telomerase and Ki67. Collectively, these observations show that TSCM cells exist in a state of perpetual flux throughout the human lifespan.
Date Issued
2016-12-13
Date Acceptance
2016-11-10
Citation
Cell Reports, 2016, 17 (11), pp.2811-2818
ISSN
2211-1247
Publisher
Elsevier
Start Page
2811
End Page
2818
Journal / Book Title
Cell Reports
Volume
17
Issue
11
Copyright Statement
© 2016 The Authors. Published by Elsevier. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Sponsor
Medical Research Council (MRC)
Commission of the European Communities
Medical Research Council (MRC)
Wellcome Trust
Leukaemia & Lymphoma Research "Beating Blood Cancers"
Bloodwise (formerly LLR)
Identifier
http://www.ncbi.nlm.nih.gov/pubmed/27974195
PII: S2211-1247(16)31595-9
Grant Number
12345-11
317040
MR/J007439/1
103865/Z/14/Z
15012
15012
Subjects
CD4(+) T cells
CD8(+) T cells
adaptive immunity
in vivo heavy water labeling
memory T cell maintenance
memory T cells
proliferation
stem cell-like memory T cells
telomerase activity
telomere length
Publication Status
Published
Coverage Spatial
United States