HIERARCHICAL INTERACTIONS OF CONTROL ELEMENTS DETERMINE CD8-ALPHA GENE-EXPRESSION IN SUBSETS OF THYMOCYTES AND PERIPHERAL T-CELLS

CD4 and CD8 are crucial for the development and function of T cells. A n intergenic deoxyribonuclease I hypersensitive site region (cluster C III) directs expression in mature CD8 T cells only. Here, we show that two further independent regions from the CD8 gene locus in conjunctio n with cluster CIII restore transgene expression in appropriate immatu re thymocytes. Deletion of two of the intergenic cluster CIII DNasel-H SS in homozygous mutant mice affects expression of CD8 alpha alpha hom odimers on intraepithelial T cells (IEL), particularly on the gamma de lta TCR+ subset. Surprisingly, none of the thymocyte or peripheral alp ha beta TCR T cell subsets are affected by this mutation, indicating h ierarchical activation of these elements within the different T cell s ubsets.