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Continuous activity of Foxo1 is required to prevent anergy and maintain the memory state of CD8(+) T cells
Upon infection with an intracellular pathogen, cytotoxic CD8(+) T cells develop diverse differentiation states characterized by function, localization, longevity, and the capacity for self-renewal. The program of differentiation is determined, in part, by FOXO1, a transcription factor known to integ...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5789410/ https://www.ncbi.nlm.nih.gov/pubmed/29282254 http://dx.doi.org/10.1084/jem.20170697 |
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author | Delpoux, Arnaud Michelini, Rodrigo Hess Verma, Shilpi Lai, Chen-Yen Omilusik, Kyla D. Utzschneider, Daniel T. Redwood, Alec J. Goldrath, Ananda W. Benedict, Chris A. Hedrick, Stephen M. |
author_facet | Delpoux, Arnaud Michelini, Rodrigo Hess Verma, Shilpi Lai, Chen-Yen Omilusik, Kyla D. Utzschneider, Daniel T. Redwood, Alec J. Goldrath, Ananda W. Benedict, Chris A. Hedrick, Stephen M. |
author_sort | Delpoux, Arnaud |
collection | PubMed |
description | Upon infection with an intracellular pathogen, cytotoxic CD8(+) T cells develop diverse differentiation states characterized by function, localization, longevity, and the capacity for self-renewal. The program of differentiation is determined, in part, by FOXO1, a transcription factor known to integrate extrinsic input in order to specify survival, DNA repair, self-renewal, and proliferation. At issue is whether the state of T cell differentiation is specified by initial conditions of activation or is actively maintained. To study the spectrum of T cell differentiation, we have analyzed an infection with mouse cytomegalovirus, a persistent-latent virus that elicits different cytotoxic T cell responses characterized as acute resolving or inflationary. Our results show that FOXO1 is continuously required for all the phenotypic characteristics of memory-effector T cells such that with acute inactivation of the gene encoding FOXO1, T cells revert to a short-lived effector phenotype, exhibit reduced viability, and manifest characteristics of anergy. |
format | Online Article Text |
id | pubmed-5789410 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-57894102018-08-05 Continuous activity of Foxo1 is required to prevent anergy and maintain the memory state of CD8(+) T cells Delpoux, Arnaud Michelini, Rodrigo Hess Verma, Shilpi Lai, Chen-Yen Omilusik, Kyla D. Utzschneider, Daniel T. Redwood, Alec J. Goldrath, Ananda W. Benedict, Chris A. Hedrick, Stephen M. J Exp Med Research Articles Upon infection with an intracellular pathogen, cytotoxic CD8(+) T cells develop diverse differentiation states characterized by function, localization, longevity, and the capacity for self-renewal. The program of differentiation is determined, in part, by FOXO1, a transcription factor known to integrate extrinsic input in order to specify survival, DNA repair, self-renewal, and proliferation. At issue is whether the state of T cell differentiation is specified by initial conditions of activation or is actively maintained. To study the spectrum of T cell differentiation, we have analyzed an infection with mouse cytomegalovirus, a persistent-latent virus that elicits different cytotoxic T cell responses characterized as acute resolving or inflationary. Our results show that FOXO1 is continuously required for all the phenotypic characteristics of memory-effector T cells such that with acute inactivation of the gene encoding FOXO1, T cells revert to a short-lived effector phenotype, exhibit reduced viability, and manifest characteristics of anergy. The Rockefeller University Press 2018-02-05 /pmc/articles/PMC5789410/ /pubmed/29282254 http://dx.doi.org/10.1084/jem.20170697 Text en © 2018 Delpoux 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 Delpoux, Arnaud Michelini, Rodrigo Hess Verma, Shilpi Lai, Chen-Yen Omilusik, Kyla D. Utzschneider, Daniel T. Redwood, Alec J. Goldrath, Ananda W. Benedict, Chris A. Hedrick, Stephen M. Continuous activity of Foxo1 is required to prevent anergy and maintain the memory state of CD8(+) T cells |
title | Continuous activity of Foxo1 is required to prevent anergy and maintain the memory state of CD8(+) T cells |
title_full | Continuous activity of Foxo1 is required to prevent anergy and maintain the memory state of CD8(+) T cells |
title_fullStr | Continuous activity of Foxo1 is required to prevent anergy and maintain the memory state of CD8(+) T cells |
title_full_unstemmed | Continuous activity of Foxo1 is required to prevent anergy and maintain the memory state of CD8(+) T cells |
title_short | Continuous activity of Foxo1 is required to prevent anergy and maintain the memory state of CD8(+) T cells |
title_sort | continuous activity of foxo1 is required to prevent anergy and maintain the memory state of cd8(+) t cells |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5789410/ https://www.ncbi.nlm.nih.gov/pubmed/29282254 http://dx.doi.org/10.1084/jem.20170697 |
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