Cytokine pattern and IgE regulation of human natural killer cells in atopic dermatitis, evidence for NK1 and NK2 subsets

Abstract

A dysregulated, cytokine mediated response of the immune system appears to be an important pathogenic factor in allergy, however, the role of natural killer (NK) cells remained unclear so far. In the present study, peripheral blood NK cells were isolated from atopic dermatitis (AD) patients and their growth requirements, cytokine pattern and IgE regulation were determined and compared with healthy controls. IL-2 and IL-15 induced efficient proliferation, but IL-4 inhibited the growth of NK cells both in AD patients and healthy individuals. Direct fixation and permeabilization of NK cells immediately after purification demonstrated that they contain and spontaneously release low amounts of IL-4 and IFN-gamma and high amounts of IL-10 and IL-16. IL-12 or IL-15 primed NK cells, in the presence of IL-2 lead to increased IFN-gamma, but decreased IL-4 production. IL-4 primed NK cells in the presence of IL-2 showed decreased IFN-gamma production, but enhanced IL-13 production. The functional immunoglobulin isotype regulatory capacity of peripheral NK cells from AD patients was investigated by co-culturing isolated NK cells subpopulations with purified B cells. NK cells. Inhibited IgE production by B cells and this was more prominent when NK cells were primed with IL-12. These results demonstrate that NK cells can differentiate into effector subsets with NK1 and NK2 phenotypes, and NK1 cells might display an anti-allergic property by inhibition of IgE production.