Transcriptional control of CD4 and CD8 coreceptor expression during T cell development
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Cellular and Molecular Life Sciences
Review
Transcriptional control of CD4 and CD8 coreceptor expression during T cell development Wilfried Ellmeier · Lena Haust · Roland Tschismarov
Received: 13 March 2013 / Revised: 27 May 2013 / Accepted: 29 May 2013 © The Author(s) 2013. This article is published with open access at Springerlink.com
Abstract The differentiation and function of peripheral helper and cytotoxic T cell lineages is coupled with the expression of CD4 and CD8 coreceptor molecules, respectively. This indicates that the control of coreceptor gene expression is closely linked with the regulation of CD4/CD8 lineage decision of DP thymocytes. Research performed during the last two decades revealed comprehensive mechanistic insight into the developmental stageand subset/lineage-specific regulation of Cd4, Cd8a and Cd8b1 (Cd8) gene expression. These studies provided important insight into transcriptional control mechanisms during T cell development and into the regulation of cisregulatory networks in general. Moreover, the identification of transcription factors involved in the regulation of CD4 and CD8 significantly advanced the knowledge of the transcription factor network regulating CD4/CD8 cell-fate choice of DP thymocytes. In this review, we provide an overview of the identification and characterization of CD4/CD8 cis-regulatory elements and present recent progress in our understanding of how these cisregulatory elements control CD4/CD8 expression during T cell development and in peripheral T cells. In addition, we describe the transcription factors implicated in the regulation of coreceptor gene expression and discuss how these factors are integrated into the transcription factor network that regulates CD4/CD8 cell-fate choice of DP thymocytes.
W. Ellmeier (*) · L. Haust · R. Tschismarov Division of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Lazarettgasse, 19, 1090 Vienna, Austria e-mail: [email protected]
Keywords T cell development · Coreceptor gene expression · Transcription factors · CD4/CD8 lineage decision
Introduction The two major subsets of peripheral T cells express either the CD4 or CD8 coreceptor molecules. CD4-expressing cells constitute MHC class II-restricted helper T cells, while CD8-expressing T cells represent MHC class I-restricted cytotoxic T cells. CD4+ and CD8+ T cells develop in the thymus from so-called double-positive (DP) thymocytes that express both CD4 and CD8. Since the helper T cell phenotype is linked with CD4 expression and since cytotoxic T cells express CD8, it was hypothesized that the regulation of coreceptor gene expression is closely interconnected with CD4/CD8 cell-fate choice of DP thymocytes. Therefore, the characterization of the molecular details of how the expression of CD4 and CD8 is regulated was a promising approach to also obtain insight into the regulation of CD4/CD8 cell-fate choice. Indeed, the identification of the cis-regulatory networks dr
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