A heritable defect in IL-12 signaling in B10.Q/J mice. I. In vitro analysis

The Journal of Immunology : Official Journal of the American Association of Immunologists
R A OrtmannE M Shevach

Abstract

B10.Q mice are normally susceptible to the induction of collagen-induced arthritis. We noted that one subline of B10.Q mice, B10.Q/J, was completely resistant to disease induction when immunized with collagen in CFA. B10.Q/J mice have a global defect in the generation of Th1 responses, and Ag-specific T cells derived from this strain failed to produce IFN-gamma. Because T cells from these mice could produce normal amounts of IFN-gamma when activated by IL-12/IL-18-independent stimuli, the defect appeared to be a failure to respond to IL-12. This defect extended to NK cells, which also failed to produce IFN-gamma when stimulated by IL-12. The capacity of NK cells, but not activated T cells, to produce IFN-gamma in response to IL-12 could be partially restored by IL-18. The expression of the IL-12R beta1- and beta2-chains on T cells and NK cells from B10.Q/J mice was normal. However, activated T cells from B10.Q/J mice did not signal normally through the IL-12R and manifested a defect in their capacity to phosphorylate Stat4. This defect was partial in that it could be overcome by increasing both the concentration of IL-12 and the incubation times in the Stat4 phosphorylation assays. Because Stat4 function is apparently intact in...Continue Reading

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Citations

Apr 21, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·G S YapA Sher
May 23, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Etsushi KurodaUki Yamashita
Apr 8, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Dong-Jun PengK Venuprasad
Jul 3, 2004·Nature Reviews. Drug Discovery·John J O'SheaPaul S Changelian
Jun 6, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michael H ShawGeorge S Yap
Apr 20, 2005·Current Opinion in Rheumatology·John J O'SheaPaul Changelian
Oct 24, 2007·Annual Review of Immunology·S M VidalP Gros
Aug 18, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marta RadwanBirgit Strobl
Aug 26, 2015·The Journal of Experimental Medicine·Alexandra Y KreinsStéphanie Boisson-Dupuis
Sep 23, 2003·Proceedings of the National Academy of Sciences of the United States of America·Michael H ShawGeorge S Yap
Nov 18, 2004·Immunological Reviews·Wendy T WatfordJohn J O'Shea
Jul 10, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Carole L SmithJoseph R Maxwell
May 25, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Masayuki IshizakiTadashi Matsuda
Jun 6, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Karen M SpachCory Teuscher
Dec 29, 2020·Journal of Medicinal Chemistry·Chunjian LiuDavid S Weinstein
Jun 30, 2010·Journal of the American Academy of Dermatology·Ricardo T PaniaguaWilliam H Robinson

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