An enhancer that directs lineage-specific expression of CD8 in positively selected thymocytes and mature T cells

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 CD8 beta and CD8 alpha 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 CD8 alpha but not CD8 beta, suggesting that it is specific for CD8 alpha 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.