Active Maintenance of T Cell Memory in Acute and Chronic Viral Infection Depends on Continuous Expression of FOXO1
Summary: Immunity following an acutely resolved infection or the long-term equipoise of chronic viral infections often depends on the maintenance of antigen-specific CD8+ T cells, yet the ongoing transcriptional requirements of these cells remain unclear. We show that active and continuous programmi...
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doaj-8d00be06d5784495b315b6323a25c4e92020-11-25T01:38:54ZengElsevierCell Reports2211-12472018-03-01221334543467Active Maintenance of T Cell Memory in Acute and Chronic Viral Infection Depends on Continuous Expression of FOXO1Daniel T. Utzschneider0Arnaud Delpoux1Dominik Wieland2Xin Huang3Chen-Yen Lai4Maike Hofmann5Robert Thimme6Stephen M. Hedrick7Molecular Biology Section, Division of Biological Sciences, UC San Diego, La Jolla, CA 92093, USA; Cellular and Molecular Medicine, UC San Diego, La Jolla, CA 92093, USA; Corresponding authorMolecular Biology Section, Division of Biological Sciences, UC San Diego, La Jolla, CA 92093, USA; Cellular and Molecular Medicine, UC San Diego, La Jolla, CA 92093, USADepartment of Medicine II, University Hospital Freiburg, 79106 Freiburg, GermanyMolecular Biology Section, Division of Biological Sciences, UC San Diego, La Jolla, CA 92093, USA; Cellular and Molecular Medicine, UC San Diego, La Jolla, CA 92093, USAMolecular Biology Section, Division of Biological Sciences, UC San Diego, La Jolla, CA 92093, USA; Cellular and Molecular Medicine, UC San Diego, La Jolla, CA 92093, USADepartment of Medicine II, University Hospital Freiburg, 79106 Freiburg, GermanyDepartment of Medicine II, University Hospital Freiburg, 79106 Freiburg, GermanyMolecular Biology Section, Division of Biological Sciences, UC San Diego, La Jolla, CA 92093, USA; Cellular and Molecular Medicine, UC San Diego, La Jolla, CA 92093, USA; Corresponding authorSummary: Immunity following an acutely resolved infection or the long-term equipoise of chronic viral infections often depends on the maintenance of antigen-specific CD8+ T cells, yet the ongoing transcriptional requirements of these cells remain unclear. We show that active and continuous programming by FOXO1 is required for the functional maintenance of a memory population. Upon Foxo1 deletion following resolution of an infection, memory cells rapidly lost their characteristic gene expression, gradually declined in number, and were impaired in self-renewal. This was extended to chronic infections, as a loss of FOXO1 during a persistent viral infection led to a rapid decline of the TCF7 (a.k.a. TCF1)-expressing memory-like subset of CD8+ T cells. We further establish FOXO1 regulation as a characteristic of human memory CD8+ T cells. Overall, we show that the molecular and functional longevity of a memory T cell population is actively maintained by the transcription factor FOXO1. : Utzschneider et al. find that hallmarks of CD8+ T cell memory such as longevity, self-renewal, and the ability to cycle between quiescence and cell division depend on continued expression of FOXO1. Loss of FOXO1 during any of these stages leads to the interruption of T cell memory. Keywords: immune memory, homeostatic proliferation, self-renewal, quiescence, cell survival, T cells, FOXO, TCF1/TCF7, chronic infection, LCMVhttp://www.sciencedirect.com/science/article/pii/S2211124718303498 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Daniel T. Utzschneider Arnaud Delpoux Dominik Wieland Xin Huang Chen-Yen Lai Maike Hofmann Robert Thimme Stephen M. Hedrick |
spellingShingle |
Daniel T. Utzschneider Arnaud Delpoux Dominik Wieland Xin Huang Chen-Yen Lai Maike Hofmann Robert Thimme Stephen M. Hedrick Active Maintenance of T Cell Memory in Acute and Chronic Viral Infection Depends on Continuous Expression of FOXO1 Cell Reports |
author_facet |
Daniel T. Utzschneider Arnaud Delpoux Dominik Wieland Xin Huang Chen-Yen Lai Maike Hofmann Robert Thimme Stephen M. Hedrick |
author_sort |
Daniel T. Utzschneider |
title |
Active Maintenance of T Cell Memory in Acute and Chronic Viral Infection Depends on Continuous Expression of FOXO1 |
title_short |
Active Maintenance of T Cell Memory in Acute and Chronic Viral Infection Depends on Continuous Expression of FOXO1 |
title_full |
Active Maintenance of T Cell Memory in Acute and Chronic Viral Infection Depends on Continuous Expression of FOXO1 |
title_fullStr |
Active Maintenance of T Cell Memory in Acute and Chronic Viral Infection Depends on Continuous Expression of FOXO1 |
title_full_unstemmed |
Active Maintenance of T Cell Memory in Acute and Chronic Viral Infection Depends on Continuous Expression of FOXO1 |
title_sort |
active maintenance of t cell memory in acute and chronic viral infection depends on continuous expression of foxo1 |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2018-03-01 |
description |
Summary: Immunity following an acutely resolved infection or the long-term equipoise of chronic viral infections often depends on the maintenance of antigen-specific CD8+ T cells, yet the ongoing transcriptional requirements of these cells remain unclear. We show that active and continuous programming by FOXO1 is required for the functional maintenance of a memory population. Upon Foxo1 deletion following resolution of an infection, memory cells rapidly lost their characteristic gene expression, gradually declined in number, and were impaired in self-renewal. This was extended to chronic infections, as a loss of FOXO1 during a persistent viral infection led to a rapid decline of the TCF7 (a.k.a. TCF1)-expressing memory-like subset of CD8+ T cells. We further establish FOXO1 regulation as a characteristic of human memory CD8+ T cells. Overall, we show that the molecular and functional longevity of a memory T cell population is actively maintained by the transcription factor FOXO1. : Utzschneider et al. find that hallmarks of CD8+ T cell memory such as longevity, self-renewal, and the ability to cycle between quiescence and cell division depend on continued expression of FOXO1. Loss of FOXO1 during any of these stages leads to the interruption of T cell memory. Keywords: immune memory, homeostatic proliferation, self-renewal, quiescence, cell survival, T cells, FOXO, TCF1/TCF7, chronic infection, LCMV |
url |
http://www.sciencedirect.com/science/article/pii/S2211124718303498 |
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