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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| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0184732&type=printable |
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| author | Kylie M Quinn Wan-Ting Kan Katherine A Watson Brian J Liddicoat Natasha G Swan Hayley McQuilten Alice E Denton Jasmine Li Weisan Chen Lorena E Brown David C Jackson Patrick C Reading Peter C Doherty Katherine Kedzierska Lukasz Kedzierski Stephen J Turner Nicole L La Gruta |
| author_facet | Kylie M Quinn Wan-Ting Kan Katherine A Watson Brian J Liddicoat Natasha G Swan Hayley McQuilten Alice E Denton Jasmine Li Weisan Chen Lorena E Brown David C Jackson Patrick C Reading Peter C Doherty Katherine Kedzierska Lukasz Kedzierski Stephen J Turner Nicole L La Gruta |
| author_sort | Kylie M Quinn |
| collection | DOAJ |
| 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. |
| format | Article |
| id | doaj-art-260e87aec1f54e8a977e6b7d40d0d4ff |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-260e87aec1f54e8a977e6b7d40d0d4ff2025-08-20T02:03:51ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01129e018473210.1371/journal.pone.0184732Extrinsically derived TNF is primarily responsible for limiting antiviral CD8+ T cell response magnitude.Kylie M QuinnWan-Ting KanKatherine A WatsonBrian J LiddicoatNatasha G SwanHayley McQuiltenAlice E DentonJasmine LiWeisan ChenLorena E BrownDavid C JacksonPatrick C ReadingPeter C DohertyKatherine KedzierskaLukasz KedzierskiStephen J TurnerNicole L La GrutaTNF 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0184732&type=printable |
| spellingShingle | Kylie M Quinn Wan-Ting Kan Katherine A Watson Brian J Liddicoat Natasha G Swan Hayley McQuilten Alice E Denton Jasmine Li Weisan Chen Lorena E Brown David C Jackson Patrick C Reading Peter C Doherty Katherine Kedzierska Lukasz Kedzierski Stephen J Turner Nicole L La Gruta Extrinsically derived TNF is primarily responsible for limiting antiviral CD8+ T cell response magnitude. PLoS ONE |
| 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 |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0184732&type=printable |
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