Regulation of IFN-γ production following 2B4 activation in human NK cells

IFN-γ is a cytokine that regulates various functions of the immune system. The major producers of IFN-γ are T cells and NK cells. 2B4 is a novel activating receptor expressed on all human NK cells, a subset of CD8+ T cells, monocytes and basophils. Activation of human NK cells through surface 2B4 enhances NK cell cytolytic function and secretion of IFN-γ. We have examined the regulation of IFN-γ production by the human NK cell line YT upon activation through surface 2B4. Our data indicate that ligation of surface 2B4 by mAb C1.7, that specifically recognizes 2B4, induces transcriptional activation of IFN-γ. Partial inhibition of transcription did not prevent the transcriptional upregulation of IFN-γ. S1 nuclease protection analysis indicated that transcriptional activation as well as mRNA stability may account for the increased production of IFN-γ by human NK cells following 2B4 stimulation.