Different natural killer (NK) receptor expression and immunoglobulin E (IgE) regulation by NK1 and NK2 cells.
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)-gamma 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-gamma and decreased IL-4. In contrast, stimulation of NK cells with IL-4 inhibited IFN-gamma, 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-gamma. 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.
Aktas
E
E
Istanbul University, Institute of Experimental Medical Research (DETAE), Istanbul, Turkey.
Akdis
M
M
Bilgic
S
S
Disch
R
R
Falk
C S
CS
Blaser
K
K
Akdis
C
C
Deniz
G
G
D000328:Adult; D017209:Apoptosis / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D003876:Dermatitis, Atopic / Q000276:immunology*; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D011971:Receptors, Immunologic / Q000378:metabolism*; D054340:Receptors, KIR
D016207:Cytokines; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D018664:Interleukin-12; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma