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Transient expression of ZBTB32 in anti-viral CD8(+) T cells limits the magnitude of the effector response and the generation of memory
Virus infections induce CD8(+) T cell responses comprised of a large population of terminal effector cells and a smaller subset of long-lived memory cells. The transcription factors regulating the relative expansion versus the long-term survival potential of anti-viral CD8(+) T cells are not complet...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5578684/ https://www.ncbi.nlm.nih.gov/pubmed/28827827 http://dx.doi.org/10.1371/journal.ppat.1006544 |
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author | Shin, Hyun Mu Kapoor, Varun N. Kim, Gwanghun Li, Peng Kim, Hang-Rae Suresh, M. Kaech, Susan M. Wherry, E. John Selin, Liisa K. Leonard, Warren J. Welsh, Raymond M. Berg, Leslie J. |
author_facet | Shin, Hyun Mu Kapoor, Varun N. Kim, Gwanghun Li, Peng Kim, Hang-Rae Suresh, M. Kaech, Susan M. Wherry, E. John Selin, Liisa K. Leonard, Warren J. Welsh, Raymond M. Berg, Leslie J. |
author_sort | Shin, Hyun Mu |
collection | PubMed |
description | Virus infections induce CD8(+) T cell responses comprised of a large population of terminal effector cells and a smaller subset of long-lived memory cells. The transcription factors regulating the relative expansion versus the long-term survival potential of anti-viral CD8(+) T cells are not completely understood. We identified ZBTB32 as a transcription factor that is transiently expressed in effector CD8(+) T cells. After acute virus infection, CD8(+) T cells deficient in ZBTB32 showed enhanced virus-specific CD8(+) T cell responses, and generated increased numbers of virus-specific memory cells; in contrast, persistent expression of ZBTB32 suppressed memory cell formation. The dysregulation of CD8(+) T cell responses in the absence of ZBTB32 was catastrophic, as Zbtb32(-/-) mice succumbed to a systemic viral infection and showed evidence of severe lung pathology. We found that ZBTB32 and Blimp-1 were co-expressed following CD8(+) T cell activation, bound to each other, and cooperatively regulated Blimp-1 target genes Eomes and Cd27. These findings demonstrate that ZBTB32 is a key transcription factor in CD8(+) effector T cells that is required for the balanced regulation of effector versus memory responses to infection. |
format | Online Article Text |
id | pubmed-5578684 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-55786842017-09-15 Transient expression of ZBTB32 in anti-viral CD8(+) T cells limits the magnitude of the effector response and the generation of memory Shin, Hyun Mu Kapoor, Varun N. Kim, Gwanghun Li, Peng Kim, Hang-Rae Suresh, M. Kaech, Susan M. Wherry, E. John Selin, Liisa K. Leonard, Warren J. Welsh, Raymond M. Berg, Leslie J. PLoS Pathog Research Article Virus infections induce CD8(+) T cell responses comprised of a large population of terminal effector cells and a smaller subset of long-lived memory cells. The transcription factors regulating the relative expansion versus the long-term survival potential of anti-viral CD8(+) T cells are not completely understood. We identified ZBTB32 as a transcription factor that is transiently expressed in effector CD8(+) T cells. After acute virus infection, CD8(+) T cells deficient in ZBTB32 showed enhanced virus-specific CD8(+) T cell responses, and generated increased numbers of virus-specific memory cells; in contrast, persistent expression of ZBTB32 suppressed memory cell formation. The dysregulation of CD8(+) T cell responses in the absence of ZBTB32 was catastrophic, as Zbtb32(-/-) mice succumbed to a systemic viral infection and showed evidence of severe lung pathology. We found that ZBTB32 and Blimp-1 were co-expressed following CD8(+) T cell activation, bound to each other, and cooperatively regulated Blimp-1 target genes Eomes and Cd27. These findings demonstrate that ZBTB32 is a key transcription factor in CD8(+) effector T cells that is required for the balanced regulation of effector versus memory responses to infection. Public Library of Science 2017-08-21 /pmc/articles/PMC5578684/ /pubmed/28827827 http://dx.doi.org/10.1371/journal.ppat.1006544 Text en © 2017 Shin et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Shin, Hyun Mu Kapoor, Varun N. Kim, Gwanghun Li, Peng Kim, Hang-Rae Suresh, M. Kaech, Susan M. Wherry, E. John Selin, Liisa K. Leonard, Warren J. Welsh, Raymond M. Berg, Leslie J. Transient expression of ZBTB32 in anti-viral CD8(+) T cells limits the magnitude of the effector response and the generation of memory |
title | Transient expression of ZBTB32 in anti-viral CD8(+) T cells limits the magnitude of the effector response and the generation of memory |
title_full | Transient expression of ZBTB32 in anti-viral CD8(+) T cells limits the magnitude of the effector response and the generation of memory |
title_fullStr | Transient expression of ZBTB32 in anti-viral CD8(+) T cells limits the magnitude of the effector response and the generation of memory |
title_full_unstemmed | Transient expression of ZBTB32 in anti-viral CD8(+) T cells limits the magnitude of the effector response and the generation of memory |
title_short | Transient expression of ZBTB32 in anti-viral CD8(+) T cells limits the magnitude of the effector response and the generation of memory |
title_sort | transient expression of zbtb32 in anti-viral cd8(+) t cells limits the magnitude of the effector response and the generation of memory |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5578684/ https://www.ncbi.nlm.nih.gov/pubmed/28827827 http://dx.doi.org/10.1371/journal.ppat.1006544 |
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