DIFFERENTIAL-EFFECTS OF THE T-HELPER CELL-TYPE 2-DERIVED CYTOKINES IL-4 AND IL-5 ON LIGAND-BINDING TO IGG AND IGA RECEPTORS EXPRESSED BY HUMAN EOSINOPHILS

Increased numbers of eosinophilic granulocytes that exhibit an activat ed phenotype are found in bronchial tissue and bronchial alveolar lava ge fluid of patients with allergic asthma, Little is known about the p rocesses that lead to activation of eosinophils in vivo, but Igs might be important stimulants. In the present study we investigated the cap acity of human eosinophils to interact with beads coated with human se rum IgC or IgA. Finding of IgC/lgA-coated beads to eosinophils from no rmal donors appeared to be dependent on priming with Th2-derived cytok ines. Priming with granulocyte-macrophage CSF, IL-4, or IL-5 is requir ed for eosinophils to form rosettes with IgA-beads. IL-4 priming resul ted in a fast and transient effect on binding of IgA-beads, whereas th e effect of IL-5 priming was slower and longer lasting. The expression of Fc alpha R (CD89) was low compared with that on neutrophils, and e xperiments with the blocking mAb My43 (CD89) showed no inhibition of r osette formation between eosinophils and IgA-coated beads. However, po lymeric myeloma IgA effectively inhibited the rosette formation of IgA -coated beads to eosinophils. Binding of IgG-beads could only be prime d with granulocyte-macrophage CSF and IL-5, not with IL-4. These data are concurrent with the hypothesis that Th2-derived cytokines spatiall y produced at the side of an allergic inflammatory response can direct eosinophils to a rather restricted primed phenotype by IL-4 or to a m ore generalized primed phenotype by IL-5.