Gene expression profiling of the human natural killer cell response to FcR activation in the presence of IL-12

The majority of NK cells (~90%) are phenotypically characterized as CD56dimCD16+, while the remaining are CD56brightCD16-. The cytotoxic CD56dimCD16+ NK subset expresses higher levels of chemokine receptors, and therefore is preferentially recruited to sites of inflammation. Encounters between CD56dimCD16+ NK cells with target cells and locally secreted inflammatory cytokines synergize to induce activation of this subset, leading to dramatically increased cytotoxic activity against target cells and abundant pro-inflammatory cytokine production often equivalent to that of the CD56brightCD16- population. The early recruitment of activation of CD56dimCD16+ NK cells to sites of inflammation raises many important questions regarding the potential immune functions of these cells that extend beyond their cytotoxic capabilities. This study has sought to elucidate the genetic profile of activated CD56dimCD16+ NK cells via a series of laboratory-based approaches coupled with a bioinformatics persective. We assessed global patterns of gene expression in CD56dimCD16+ human NK cells following FcR stimulation in the presence or absence of the potent immune-stimulatory cytokine, IL-12, as compared to non-stimulated (medium) control samples.