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Human memory CD8 T cell effector potential is epigenetically preserved during in vivo homeostasis

Antigen-independent homeostasis of memory CD8 T cells is vital for sustaining long-lived T cell–mediated immunity. In this study, we report that maintenance of human memory CD8 T cell effector potential during in vitro and in vivo homeostatic proliferation is coupled to preservation of acquired DNA...

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Autores principales: Abdelsamed, Hossam A., Moustaki, Ardiana, Fan, Yiping, Dogra, Pranay, Ghoneim, Hazem E., Zebley, Caitlin C., Triplett, Brandon M., Sekaly, Rafick-Pierre, Youngblood, Ben
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5461005/
https://www.ncbi.nlm.nih.gov/pubmed/28490440
http://dx.doi.org/10.1084/jem.20161760
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author Abdelsamed, Hossam A.
Moustaki, Ardiana
Fan, Yiping
Dogra, Pranay
Ghoneim, Hazem E.
Zebley, Caitlin C.
Triplett, Brandon M.
Sekaly, Rafick-Pierre
Youngblood, Ben
author_facet Abdelsamed, Hossam A.
Moustaki, Ardiana
Fan, Yiping
Dogra, Pranay
Ghoneim, Hazem E.
Zebley, Caitlin C.
Triplett, Brandon M.
Sekaly, Rafick-Pierre
Youngblood, Ben
author_sort Abdelsamed, Hossam A.
collection PubMed
description Antigen-independent homeostasis of memory CD8 T cells is vital for sustaining long-lived T cell–mediated immunity. In this study, we report that maintenance of human memory CD8 T cell effector potential during in vitro and in vivo homeostatic proliferation is coupled to preservation of acquired DNA methylation programs. Whole-genome bisulfite sequencing of primary human naive, short-lived effector memory (T(EM)), and longer-lived central memory (T(CM)) and stem cell memory (T(SCM)) CD8 T cells identified effector molecules with demethylated promoters and poised for expression. Effector-loci demethylation was heritably preserved during IL-7– and IL-15–mediated in vitro cell proliferation. Conversely, cytokine-driven proliferation of T(CM) and T(SCM) memory cells resulted in phenotypic conversion into T(EM) cells and was coupled to increased methylation of the CCR7 and Tcf7 loci. Furthermore, haploidentical donor memory CD8 T cells undergoing in vivo proliferation in lymphodepleted recipients also maintained their effector-associated demethylated status but acquired T(EM)-associated programs. These data demonstrate that effector-associated epigenetic programs are preserved during cytokine-driven subset interconversion of human memory CD8 T cells.
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spelling pubmed-54610052017-12-05 Human memory CD8 T cell effector potential is epigenetically preserved during in vivo homeostasis Abdelsamed, Hossam A. Moustaki, Ardiana Fan, Yiping Dogra, Pranay Ghoneim, Hazem E. Zebley, Caitlin C. Triplett, Brandon M. Sekaly, Rafick-Pierre Youngblood, Ben J Exp Med Research Articles Antigen-independent homeostasis of memory CD8 T cells is vital for sustaining long-lived T cell–mediated immunity. In this study, we report that maintenance of human memory CD8 T cell effector potential during in vitro and in vivo homeostatic proliferation is coupled to preservation of acquired DNA methylation programs. Whole-genome bisulfite sequencing of primary human naive, short-lived effector memory (T(EM)), and longer-lived central memory (T(CM)) and stem cell memory (T(SCM)) CD8 T cells identified effector molecules with demethylated promoters and poised for expression. Effector-loci demethylation was heritably preserved during IL-7– and IL-15–mediated in vitro cell proliferation. Conversely, cytokine-driven proliferation of T(CM) and T(SCM) memory cells resulted in phenotypic conversion into T(EM) cells and was coupled to increased methylation of the CCR7 and Tcf7 loci. Furthermore, haploidentical donor memory CD8 T cells undergoing in vivo proliferation in lymphodepleted recipients also maintained their effector-associated demethylated status but acquired T(EM)-associated programs. These data demonstrate that effector-associated epigenetic programs are preserved during cytokine-driven subset interconversion of human memory CD8 T cells. The Rockefeller University Press 2017-06-05 /pmc/articles/PMC5461005/ /pubmed/28490440 http://dx.doi.org/10.1084/jem.20161760 Text en © 2017 Abdelsamed et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Abdelsamed, Hossam A.
Moustaki, Ardiana
Fan, Yiping
Dogra, Pranay
Ghoneim, Hazem E.
Zebley, Caitlin C.
Triplett, Brandon M.
Sekaly, Rafick-Pierre
Youngblood, Ben
Human memory CD8 T cell effector potential is epigenetically preserved during in vivo homeostasis
title Human memory CD8 T cell effector potential is epigenetically preserved during in vivo homeostasis
title_full Human memory CD8 T cell effector potential is epigenetically preserved during in vivo homeostasis
title_fullStr Human memory CD8 T cell effector potential is epigenetically preserved during in vivo homeostasis
title_full_unstemmed Human memory CD8 T cell effector potential is epigenetically preserved during in vivo homeostasis
title_short Human memory CD8 T cell effector potential is epigenetically preserved during in vivo homeostasis
title_sort human memory cd8 t cell effector potential is epigenetically preserved during in vivo homeostasis
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5461005/
https://www.ncbi.nlm.nih.gov/pubmed/28490440
http://dx.doi.org/10.1084/jem.20161760
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