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 involv es complex regulation of coreceptor gene expression. By analyzing expr ession of a reporter gene in transgenic mice, we have identified a DNA segment, located between the murine CD8 beta and CD8 alpha genes, tha t has enhancer activity restricted to CD8 lineage cells. Remarkably, t his enhancer functions in thymocytes undergoing positive selection to the CD4(-)CD8(+) phenotype but not in immature double-positive thymocy tes. The enhancer also functions in gut intraepithelial lymphocytes th at 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 i mplications for understanding the mechanism of lineage commitment in t hymocytes.