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Reduced Interleukin-4 Receptor α Expression on CD8(+) T Cells Correlates with Higher Quality Anti-Viral Immunity

tetano

Editor, Senior Moderator
PLoS One. 2013;8(1):e55788. doi: 10.1371/journal.pone.0055788. Epub 2013 Jan 31.
Reduced Interleukin-4 Receptor α Expression on CD8(+) T Cells Correlates with Higher Quality Anti-Viral Immunity.
Wijesundara DK, Tscharke DC, Jackson RJ, Ranasinghe C.
Source

The Molecular Mucosal Vaccine Immunology Group, The Department of Immunology, The John Curtin School of Medical Research, The Australian National University, Acton, Canberra, Australia.
Abstract

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.

PMID:
23383283
[PubMed - in process]
PMCID:
PMC3561338

Free full text

http://www.ncbi.nlm.nih.gov/pubmed/23383283
 
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