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)) that directs expression in mature CD8 single-positive thymocytes and peripheral CD8(+) T cells and in extrathymically derived intestinal intraepithelial lymphocytes (IEL). in this study, we show that deletion of E8(l) by homologous recombination results in reduced CD8 alpha alpha homodimer expression on IEL. Since CD8 expression on thymus-derived T cells was normal, other enhancers regulate CD8 expression in these cells. By exploiting a transgenic reporter expression assay, we identified three additional enhancers that directed expression in diverse thymocyte 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.