PMID: 15383578Sep 24, 2004Paper

Ikaros null mice display defects in T cell selection and CD4 versus CD8 lineage decisions

The Journal of Immunology : Official Journal of the American Association of Immunologists
Julie A Urban, Susan Winandy

Abstract

Previous evidence suggested that the hemopoietic-specific nuclear factor Ikaros regulates TCR signaling thresholds in mature T cells. In this study, we test the hypothesis that Ikaros also sets TCR signaling thresholds to regulate selection events and CD4 vs CD8 lineage determination in developing thymocytes. Ikaros null mice were crossed to three lines of TCR-transgenic mice, and positive selection, negative selection, and CD4 vs CD8 lineage decisions were analyzed. Mice expressing a polyclonal repertoire or a MHC class II-restricted TCR transgene exhibited enhanced positive selection toward the CD4 lineage. Moreover, in the absence of Ikaros, CD4 development can occur with decreased thresholds of TCR signaling. In addition, CD4 single-positive thymocytes were detected in MHC class I-restricted TCR-transgenic Ikaros null mice. To assess the role of Ikaros in negative selection, we analyzed deletion of T cells induced by conventional Ag or by endogenous superantigen. Surprisingly, negative selection was impaired in Ikaros null thymocytes despite evidence of high levels of TCR signal and no intrinsic defect in apoptosis ex vivo. To our knowledge, these data identify Ikaros as the first nuclear factor that plays a critical role i...Continue Reading

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Citations

Mar 18, 2005·Annual Review of Immunology·Ellen V Rothenberg, Tom Taghon
Feb 2, 2006·Immunological Reviews·Parinaz Aliahmad, Jonathan Kaye
Oct 23, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sheila Chari, Susan Winandy
Mar 21, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Julie A UrbanSusan Winandy
Aug 12, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ariadne L Hager-TheodoridesTessa Crompton
Jul 19, 2011·World Journal of Biological Chemistry·Maclean SellarsSusan Chan
Jan 10, 2013·European Journal of Immunology·Susan Winandy
Sep 20, 2008·Nature Reviews. Immunology·Alfred SingerJung-Hyun Park
Nov 10, 2015·Nature Communications·Attila OraveczPhilippe Kastner
Oct 5, 2013·Blood·Naomi Taylor, Valérie S Zimmermann
Nov 18, 2015·The Journal of Experimental Medicine·Pengyan XiaZusen Fan
Aug 5, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michael SchorppThomas Boehm
Feb 22, 2008·The Journal of Biological Chemistry·Katie L KathreinSusan Winandy
Jan 13, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Carolina Lyon de AnaSusan Winandy
Apr 16, 2005·Journal of Cellular Biochemistry·Susan Winandy
Jul 22, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Qi CaiPhilippe Kastner
Dec 18, 2010·Cytokine·Michael J Shapiro, Virginia Smith Shapiro

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