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 stage- and 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 cis-regulatory 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 cis-regulatory 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.
Highlights
The two major subsets of peripheral T cells express either the CD4 or CD8 coreceptor molecules
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
The identification of transcription factors involved in the transcriptional regulation of CD4 and CD8 significantly advanced the knowledge about the transcription factor network regulating CD4/CD8 cell-fate choice of DP thymocytes
Summary
The two major subsets of peripheral T cells express either the CD4 or CD8 coreceptor molecules. Those DP thymocytes that were able to activate the Cd8ab gene complex expressed normal levels of CD8, indicating that other cis-regulatory elements maintain CD8 expression and/or that epigenetic mechanisms are involved in the regulation of CD8 expression in mature CD8+ T cells.
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