HUMAN CD8-ALPHA EXPRESSION IN NK CELLS BUT NOT CYTOTOXIC T-CELLS OF TRANSGENIC MICE

In our previous work, DNase hypersensitivity mapping was used to ident ify an enhancer within the human CD8 alpha (hCD8 alpha) gene which all owed T cell-specific expression of a reporter construct in transiently transfected cell lines, To study the role of this intronic enhancer i n vivo, transgenic mice were made using human CD8 genomic constructs, We found that while a 14 kb wild-type human CD8 alpha (WThCD8) genomic construct did not lead to expression in mature peripheral CD8(+) T ce lls, this transgene was consistently expressed in small populations of T cells and B cells, and in a subset of mouse NK cells, While murine CD8 is not normally expressed on resting NK cells, expression of the h uman CD8 transgene on mouse NK cells is appropriate since CD8 is expre ssed on a subset of human NK cells, Deletion of the intronic enhancer resulted in a complete loss of transgene expression in most lines and a loss of expression only in NK cells in one line. Our results indicat e, firstly, that cis-acting sequences within the 14 kb genomic fragmen t are sufficient for NK cell-specific expression, In addition, our res ults suggest that the enhancer may have dual roles in regulation of tr ansgene expression, It may enhance general expression of the transgene and may also be required for NK cell-specific expression.