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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
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.
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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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