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C Akdis

Publications and source records attributed to C Akdis.

4 recordsLinked to original sources
PubMed2005

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.

Adult↗
PubMed1998

Determinants and mechanisms of human immune responses to bee venom phospholipase A2.

The elicitation of an immune response to protein antigens depends on the specific recognition of antigenic determinants (epitopes) by T and B lymphocytes. Bee venom phospholipase A2 (PLA) represents the major antigen/allergen of honey bee venom. It displays three dominant immunogenic peptide and one glycopeptide T cell recognition sites. These epitopes are equally recognized by both allergic and nonallergic individuals. A mixture of the three epitope containing peptides was successfully used in specific immunotherapy of bee venom-allergic patients. Both peptide and whole bee venom immunotherapy induced a state of specific anergy in T cells. The production of specific IgE and IgG4 antibodies directly correlated with the secreted interleukin-4:gamma-interferon (IL-4:IFNgamma) ratio, which itself depended on the concentration of available antigen and the strength of the T cell-activating signal. This signal comprises accumulated molecular interactions delivered by engagement of the antigenic peptide/MHC class II complex with the T cell receptor (TcR). Indeed the thermodynamic laws of chemical equilibrium reactions reveal that the antigen concentration, together with the equilibration constant Ki and the related Gibbs standard free energy DeltaG degrees of the MHC-II/Ag/TcR complex reaction, may govern the secreted IL-4:IFNgamma ratio, and in consequence, differential IgE and IgG4 antibody formation. Ki includes epitope and MHC-II haplotype variability and therefore represents a measure of immunological individuality. A major B cell epitope was determined by using point-mutated PLA. Specific antigen recognition by B cells can trigger distinct cytokine profiles in T cells and contribute to the differential regulation of specific IgE and IgG4 antibodies. Our results indicate that distinct cytokine profiles inducing allergic and nonallergic responses can be attributed to thresholds of T cell activation generated by the specific binding properties of individual MHC-II molecules to immunogenic T cell epitopes and their presentation to TcR.

Allergens↗
PubMed1994

Chemiluminescent and enzyme-linked immuno assays for sensitive detection of human IFN-gamma.

We have produced and characterized 4 mAbs to human IFN-gamma and established sensitive, non-radioactive immuno-assays. The first two assays use microtiter plates as the solid phase and enzymes or chemiluminescence (acridinium ester) for development. The use of chemiluminescence instead of peroxidase increased the sensitivity of the assay by a factor of about 75. The third and the fourth assays utilize polystyrene beads as the solid phase and enzymes or acridinium ester for development. The use of beads also increased the sensitivity of detection. The most sensitive IFN-gamma detection was achieved by the combination of bead with acridinium ester. In this configuration we were able to detect about 0.2 pg/ml IFN-gamma (1/250th of a unit). These chemiluminescent immunoassays (CLIA) appear to be more sensitive than existing ELISAs or radioimmunoassays and may find new application areas.

Animals↗