Abstract
Developmental stage-, subset-, and lineage-specific CD8 enhancers have been identified recently by transgenic reporter analyses. Enhancer E8 II (CIV-4,5) is active in both immature double-positive thymocytes (DP) and mature CD8 single-positive (SP) thymocytes and T cells, whereas E8 I (CIII-1,2) directs expression only in mature cells. In mice lacking either E8 I (CIII-1,2) or E8 II (CIV-4,5), there was no effect on CD8 expression in DP thymocytes. However, deletion of both enhancers resulted in variegated expression of CD8, with appearance of CD4 +CD8 − SP thymocytes expressing surface markers characteristic of DP thymocytes. Consequently, fewer mature CD8 + T cells developed from the reduced pool of DP cells. These results suggest that the initiation of CD8 expression is mediated by cis-regulatory elements that are distinct from any that may be involved in maintenance of expression.
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