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Extrinsically derived TNF is primarily responsible for limiting antiviral CD8+ T cell response magnitude

TNF is a pro-inflammatory cytokine produced by both lymphoid and non-lymphoid cells. As a consequence of the widespread expression of its receptors (TNFR1 and 2), TNF plays a role in many important biological processes. In the context of influenza A virus (IAV) infection, TNF has variably been impli...

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Autores principales: Quinn, Kylie M., Kan, Wan-Ting, Watson, Katherine A., Liddicoat, Brian J., Swan, Natasha G., McQuilten, Hayley, Denton, Alice E., Li, Jasmine, Chen, Weisan, Brown, Lorena E., Jackson, David C., Reading, Patrick C., Doherty, Peter C., Kedzierska, Katherine, Kedzierski, Lukasz, Turner, Stephen J., La Gruta, Nicole L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5590991/
https://www.ncbi.nlm.nih.gov/pubmed/28886201
http://dx.doi.org/10.1371/journal.pone.0184732
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author Quinn, Kylie M.
Kan, Wan-Ting
Watson, Katherine A.
Liddicoat, Brian J.
Swan, Natasha G.
McQuilten, Hayley
Denton, Alice E.
Li, Jasmine
Chen, Weisan
Brown, Lorena E.
Jackson, David C.
Reading, Patrick C.
Doherty, Peter C.
Kedzierska, Katherine
Kedzierski, Lukasz
Turner, Stephen J.
La Gruta, Nicole L.
author_facet Quinn, Kylie M.
Kan, Wan-Ting
Watson, Katherine A.
Liddicoat, Brian J.
Swan, Natasha G.
McQuilten, Hayley
Denton, Alice E.
Li, Jasmine
Chen, Weisan
Brown, Lorena E.
Jackson, David C.
Reading, Patrick C.
Doherty, Peter C.
Kedzierska, Katherine
Kedzierski, Lukasz
Turner, Stephen J.
La Gruta, Nicole L.
author_sort Quinn, Kylie M.
collection PubMed
description TNF is a pro-inflammatory cytokine produced by both lymphoid and non-lymphoid cells. As a consequence of the widespread expression of its receptors (TNFR1 and 2), TNF plays a role in many important biological processes. In the context of influenza A virus (IAV) infection, TNF has variably been implicated in mediating immunopathology as well as suppression of the immune response. Although a number of cell types are able to produce TNF, the ability of CD8(+) T cells to produce TNF following viral infection is a hallmark of their effector function. As such, the regulation and role of CD8(+) T cell-derived TNF following viral infection is of great interest. Here, we show that the biphasic production of TNF by CD8(+) T cells following in vitro stimulation corresponds to distinct patterns of epigenetic modifications. Further, we show that a global loss of TNF during IAV infection results in an augmentation of the peripheral virus-specific CD8(+) T cell response. Subsequent adoptive transfer experiments demonstrated that this attenuation of the CD8(+) T cell response was largely, but not exclusively, conferred by extrinsic TNF, with intrinsically-derived TNF making only modest contributions. In conclusion, TNF exerts an immunoregulatory role on CD8(+) T cell responses following IAV infection, an effect that is largely mediated by extrinsically-derived TNF.
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spelling pubmed-55909912017-09-15 Extrinsically derived TNF is primarily responsible for limiting antiviral CD8+ T cell response magnitude Quinn, Kylie M. Kan, Wan-Ting Watson, Katherine A. Liddicoat, Brian J. Swan, Natasha G. McQuilten, Hayley Denton, Alice E. Li, Jasmine Chen, Weisan Brown, Lorena E. Jackson, David C. Reading, Patrick C. Doherty, Peter C. Kedzierska, Katherine Kedzierski, Lukasz Turner, Stephen J. La Gruta, Nicole L. PLoS One Research Article TNF is a pro-inflammatory cytokine produced by both lymphoid and non-lymphoid cells. As a consequence of the widespread expression of its receptors (TNFR1 and 2), TNF plays a role in many important biological processes. In the context of influenza A virus (IAV) infection, TNF has variably been implicated in mediating immunopathology as well as suppression of the immune response. Although a number of cell types are able to produce TNF, the ability of CD8(+) T cells to produce TNF following viral infection is a hallmark of their effector function. As such, the regulation and role of CD8(+) T cell-derived TNF following viral infection is of great interest. Here, we show that the biphasic production of TNF by CD8(+) T cells following in vitro stimulation corresponds to distinct patterns of epigenetic modifications. Further, we show that a global loss of TNF during IAV infection results in an augmentation of the peripheral virus-specific CD8(+) T cell response. Subsequent adoptive transfer experiments demonstrated that this attenuation of the CD8(+) T cell response was largely, but not exclusively, conferred by extrinsic TNF, with intrinsically-derived TNF making only modest contributions. In conclusion, TNF exerts an immunoregulatory role on CD8(+) T cell responses following IAV infection, an effect that is largely mediated by extrinsically-derived TNF. Public Library of Science 2017-09-08 /pmc/articles/PMC5590991/ /pubmed/28886201 http://dx.doi.org/10.1371/journal.pone.0184732 Text en © 2017 Quinn 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
Quinn, Kylie M.
Kan, Wan-Ting
Watson, Katherine A.
Liddicoat, Brian J.
Swan, Natasha G.
McQuilten, Hayley
Denton, Alice E.
Li, Jasmine
Chen, Weisan
Brown, Lorena E.
Jackson, David C.
Reading, Patrick C.
Doherty, Peter C.
Kedzierska, Katherine
Kedzierski, Lukasz
Turner, Stephen J.
La Gruta, Nicole L.
Extrinsically derived TNF is primarily responsible for limiting antiviral CD8+ T cell response magnitude
title Extrinsically derived TNF is primarily responsible for limiting antiviral CD8+ T cell response magnitude
title_full Extrinsically derived TNF is primarily responsible for limiting antiviral CD8+ T cell response magnitude
title_fullStr Extrinsically derived TNF is primarily responsible for limiting antiviral CD8+ T cell response magnitude
title_full_unstemmed Extrinsically derived TNF is primarily responsible for limiting antiviral CD8+ T cell response magnitude
title_short Extrinsically derived TNF is primarily responsible for limiting antiviral CD8+ T cell response magnitude
title_sort extrinsically derived tnf is primarily responsible for limiting antiviral cd8+ t cell response magnitude
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5590991/
https://www.ncbi.nlm.nih.gov/pubmed/28886201
http://dx.doi.org/10.1371/journal.pone.0184732
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