title: Reduced interleukin-4 receptor α expression on CD8+ T cells correlates with higher quality anti-viral immunity.
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.
authors: The Molecular Mucosal Vaccine Immunology Group, The Department of Immunology, The John Curtin School of Medical Research, The Australian National University, Acton, Canberra, Australia. danushka.wijesundara@anu.edu.au
authors: Danushka K
authors: DK
authors: Wijesundara
authors: David C
authors: DC
authors: Tscharke
authors: Ronald J
authors: RJ
authors: Jackson
authors: Charani
authors: C
authors: Ranasinghe
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D018793:Interleukin-13 / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D053662:Interleukin-4 Receptor alpha Subunit / Q000235:genetics / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D053660:Receptors, Interleukin-13 / Q000235:genetics / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000235:genetics / Q000378:metabolism; D014615:Vaccinia / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D014616:Vaccinia virus / Q000276:immunology*
chemical_list: D018793:Interleukin-13; D053662:Interleukin-4 Receptor alpha Subunit; D053660:Receptors, Interleukin-13; D050800:STAT6 Transcription Factor; D015847:Interleukin-4; D007371:Interferon-gamma
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