An Enhancer That Directs Lineage-Specific Expression of CD8 in Positively Selected Thymocytes and Mature T Cells

Abstract

Positive selection of CD4+CD8+ T cells to the CD4+CD8− helper and CD4−CD8+ cytotoxic lineages is a multistep process that involves complex regulation of coreceptor gene expression. By analyzing expression of a reporter gene in transgenic mice, we have identified a DNA segment, located between the murine CD8β and CD8α genes, that has enhancer activity restricted to CD8 lineage cells. Remarkably, this enhancer functions in thymocytes undergoing positive selection to the CD4−CD8+ phenotype but not in immature double-positive thymocytes. The enhancer also functions in gut intraepithelial lymphocytes that express CD8α but not CD8β, suggesting that it is specific for CD8α expression. The tight correlation between activation of this enhancer and the final step in positive selection has important implications for understanding the mechanism of lineage commitment in thymocytes.