Human CD8α expression in NK cells but not cytotoxic T cells of transgenic mice

Abstract

In our previous work, DNase hypersensitivity mapping was used to identify an enhancer within the human CD8 alpha (hCD8 alpha) gene which allowed T cell-specific expression of a reporter construct in transiently transfected cell lines. To study the role of this intronic enhancer in 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 cells, 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 human CD8 transgene on mouse NK cells is appropriate since CD8 is expressed 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 indicate, firstly, that cis-acting sequences within the 14 kb genomic fragment are sufficient for NK cell-specific expression. In addition, our results suggest that the enhancer may have dual roles in regulation of transgene expression. It may enhance general expression of the transgene and may also be required for NK cell-specific expression.

High Frequencies of Polyfunctional CD8+NK Cells in Chronic HIV-1 Infection Are Associated with Slower Disease Progression

“…Furthermore, our data emphasize that a better understanding of the precise role of CD8 on human NK cells is required. The surface expression of the homodimer CD8␣␣ on NK cells was observed in rats (47) and pigs (48) but was reported to be absent in mice (49) and thus seems to vary across different mammalian species (50). In rhesus macaques, one of the best-studied nonhuman primate models, virtually all NK cells express CD8 (28,51,52).…”

CD4 and CD8: an inside-out coreceptor model for innate immune cells

“…Although CD8 is found on DC and T cells in all species [24 -26], it is only in rat and human that CD8 is found on a variety of other immune cells. Current evidence suggests that CD8␣ protein is expressed by NK cells in rat [27] and human [28] but not in mouse [29] ( Table 1 and references therein). Similarly rat [42,44] and human monocytes [31] and macrophages [35] express CD8␣, and the same cells in the mouse lack CD8␣ [33].…”

Description of an Ectothermic TCR Coreceptor, CD8α, in Rainbow Trout

“…A putative T cell-specific enhancer was later found in the last intron of the CD8␣ gene, located near a large stem loop structure (34,35). When introduced into transgenic mice, this enhancer region was able to drive expression in an NK cell-specific manner, which may be related to the usage of CD8␣␣ homodimers for this cell type (36). Within the trout locus, several regulatory motifs implicated in cellular immunity were found within the introns including binding sites for c-ets, GATA-3, and Ikaros (Fig.…”