Different natural killer (NK) receptor expression and immunoglobulin E (IgE) regulation by NK1 and NK2 cells

Summary Many studies concerning the role of T cells and cytokines in allergy have been performed, but little is known about the role of natural killer (NK) cells. Accordingly, the expression of co‐stimulatory, inhibitory and apoptosis receptors, cytokine profiles and their effect on immunoglobulin isotypes were investigated in polyallergic atopic dermatitis (AD) patients with hyper immunoglobulin E (IgE) and healthy individuals. AD patients showed significantly decreased peripheral blood NK cells compared to healthy individuals. Freshly isolated NK cells of polyallergic patients spontaneously released higher amounts of interleukin (IL)‐4, IL‐5, IL‐13 and interferon (IFN)‐γ compared to healthy individuals. NK cells were differentiated to NK1 cells by IL‐12 and neutralizing anti‐IL‐4 monoclonal antibodies (mAb), and to NK2 cells by IL‐4 and neutralizing anti‐IL‐12 mAb. Following IL‐12 stimulation, NK cells produced increased levels of IFN‐γ and decreased IL‐4. In contrast, stimulation of NK cells with IL‐4 inhibited IFN‐γ, but increased IL‐13, production. The effect of NK cell subsets on IgE regulation was examined in co‐cultures of in vitro differentiated NK cells with peripheral blood mononuclear cells (PBMC) or B cells. NK1 cells significantly inhibited IL‐4‐ and soluble CD40‐ligand‐stimulated IgE production; however, NK2 cells did not have any effect. The inhibitory effect of NK1 cells on IgE production was blocked by neutralization of IFN‐γ. Except for CD40, NK cell subsets showed different expression of killer‐inhibitory receptors and co‐stimulatory molecules between the polyallergic and healthy subjects. These results indicate that human NK cells show differences in numbers, surface receptor and cytokine phenotypes and functional properties in AD.