MULTIPLE DEVELOPMENTAL STAGE-SPECIFIC ENHANCERS REGULATE CD8 EXPRESSION IN DEVELOPING THYMOCYTES AND IN THYMUS-INDEPENDENT T-CELLS

We and others have recently identified a CD8 locus enhancer (E8(l)) th at directs expression in mature CD8 single-positive thymocytes and per ipheral CD8(+) T cells and in extrathymically derived intestinal intra epithelial lymphocytes (IEL). in this study, we show that deletion of E8(l) by homologous recombination results in reduced CD8 alpha alpha h omodimer expression on IEL. Since CD8 expression on thymus-derived T c ells was normal, other enhancers regulate CD8 expression in these cell s. By exploiting a transgenic reporter expression assay, we identified three additional enhancers that directed expression in diverse thymoc yte subsets and mature T cells but not in CD8 alpha alpha(+) IEL. The results suggest that CD8 alpha expression is primarily regulated by E8 (l) in IEL and by the novel enhancers in the thymus-dependent lineages .