Reduced interleukin-4 receptor α expression on CD8+ T cells correlates with higher quality anti-viral immunity.

With the hope of understanding how interleukin (IL)-4 and IL-13 modulated quality of anti-viral CD8(+) T cells, we evaluated the expression of receptors for these cytokines following a range of viral infections (e.g. pox viruses and influenza virus). Results clearly indicated that unlike other IL-4/...

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Main Authors: Danushka K Wijesundara, David C Tscharke, Ronald J Jackson, Charani Ranasinghe
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3561338?pdf=render
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author Danushka K Wijesundara
David C Tscharke
Ronald J Jackson
Charani Ranasinghe
author_facet Danushka K Wijesundara
David C Tscharke
Ronald J Jackson
Charani Ranasinghe
author_sort Danushka K Wijesundara
collection DOAJ
description With the hope of understanding how interleukin (IL)-4 and IL-13 modulated quality of anti-viral CD8(+) T cells, we evaluated the expression of receptors for these cytokines following a range of viral infections (e.g. pox viruses and influenza virus). Results clearly indicated that unlike other IL-4/IL-13 receptor subunits, IL-4 receptor α (IL-4Rα) was significantly down-regulated on anti-viral CD8(+) T cells in a cognate antigen dependent manner. The infection of gene knockout mice and wild-type (WT) mice with vaccinia virus (VV) or VV expressing IL-4 confirmed that IL-4, IL-13 and signal transducer and activator of transcription 6 (STAT6) were required to increase IL-4Rα expression on CD8(+) T cells, but not interferon (IFN)-γ. STAT6 dependent elevation of IL-4Rα expression on CD8(+) T cells was a feature of poor quality anti-viral CD8(+) T cell immunity as measured by the production of IFN-γ and tumor necrosis factor α (TNF-α) in response to VV antigen stimulation in vitro. We propose that down-regulation of IL-4Rα, but not the other IL-4/IL-13 receptor subunits, is a mechanism by which CD8(+) T cells reduce responsiveness to IL-4 and IL-13. This can improve the quality of anti-viral CD8(+) T cell immunity. Our findings have important implications in understanding anti-viral CD8(+) T cell immunity and designing effective vaccines against chronic viral infections.
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spelling doaj.art-80c343fe4a3a4345bf62ebef52d3271a2022-12-22T03:16:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0181e5578810.1371/journal.pone.0055788Reduced interleukin-4 receptor α expression on CD8+ T cells correlates with higher quality anti-viral immunity.Danushka K WijesundaraDavid C TscharkeRonald J JacksonCharani RanasingheWith the hope of understanding how interleukin (IL)-4 and IL-13 modulated quality of anti-viral CD8(+) T cells, we evaluated the expression of receptors for these cytokines following a range of viral infections (e.g. pox viruses and influenza virus). Results clearly indicated that unlike other IL-4/IL-13 receptor subunits, IL-4 receptor α (IL-4Rα) was significantly down-regulated on anti-viral CD8(+) T cells in a cognate antigen dependent manner. The infection of gene knockout mice and wild-type (WT) mice with vaccinia virus (VV) or VV expressing IL-4 confirmed that IL-4, IL-13 and signal transducer and activator of transcription 6 (STAT6) were required to increase IL-4Rα expression on CD8(+) T cells, but not interferon (IFN)-γ. STAT6 dependent elevation of IL-4Rα expression on CD8(+) T cells was a feature of poor quality anti-viral CD8(+) T cell immunity as measured by the production of IFN-γ and tumor necrosis factor α (TNF-α) in response to VV antigen stimulation in vitro. We propose that down-regulation of IL-4Rα, but not the other IL-4/IL-13 receptor subunits, is a mechanism by which CD8(+) T cells reduce responsiveness to IL-4 and IL-13. This can improve the quality of anti-viral CD8(+) T cell immunity. Our findings have important implications in understanding anti-viral CD8(+) T cell immunity and designing effective vaccines against chronic viral infections.http://europepmc.org/articles/PMC3561338?pdf=render
spellingShingle Danushka K Wijesundara
David C Tscharke
Ronald J Jackson
Charani Ranasinghe
Reduced interleukin-4 receptor α expression on CD8+ T cells correlates with higher quality anti-viral immunity.
PLoS ONE
title Reduced interleukin-4 receptor α expression on CD8+ T cells correlates with higher quality anti-viral immunity.
title_full Reduced interleukin-4 receptor α expression on CD8+ T cells correlates with higher quality anti-viral immunity.
title_fullStr Reduced interleukin-4 receptor α expression on CD8+ T cells correlates with higher quality anti-viral immunity.
title_full_unstemmed Reduced interleukin-4 receptor α expression on CD8+ T cells correlates with higher quality anti-viral immunity.
title_short Reduced interleukin-4 receptor α expression on CD8+ T cells correlates with higher quality anti-viral immunity.
title_sort reduced interleukin 4 receptor α expression on cd8 t cells correlates with higher quality anti viral immunity
url http://europepmc.org/articles/PMC3561338?pdf=render
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AT davidctscharke reducedinterleukin4receptoraexpressiononcd8tcellscorrelateswithhigherqualityantiviralimmunity
AT ronaldjjackson reducedinterleukin4receptoraexpressiononcd8tcellscorrelateswithhigherqualityantiviralimmunity
AT charaniranasinghe reducedinterleukin4receptoraexpressiononcd8tcellscorrelateswithhigherqualityantiviralimmunity