[Polynuclear basophils, the key to allergic reactions. Modulations by chemokines]

Both IgE synthesis and inflammatory cell recruitment are recognized to be major components of the allergic response, leading to bronchial inflammation. Typically, T cells are considered to be the key stone of the allergic reaction after acquisition of their TH2 phenotype, responsible for IL-4, -5, -10 -13 production. Basophil is also capable to produce IL-4 and IL-13 following non-specific or antigen activations, and chemokines induce basophil chemotaxis and inflammatory mediator release. However, in context of allergy, the contribution of basophil to cytokine production remains unclear, and the role of chemokine on it is not known. To address this issue, leucocytes from healthy and allergic asthmatic patients were incubated in presence of ionomycine or Ag extracts, with or without chemokine, then fixed, permeabilized, stained using antibodies anti-IgE, anti-CD3, anti-cytokine, and analyzed by flow cytometry. After ionomycin activation, a large majority of basophils from both control and allergic asthmatic subjects express IL-4 and IL-13. Specific antigen induce cytokine expression by 5-20% of basophils from the asthmatic group only, and basophils represent 80% of IL-4 producing cells (p < 0.01). Basophil IL-4 expression peaks at 2 h (p < 0.01), whereas IL-13 expression is more delayed, suggesting that basophil may be involved in initiation, amplification and maintenance of allergic response. Since CD40 ligand is early up-regulated on peripheral blood basophils (p < 0.05), it may be critical in the initial IgE production. CC chemokines (eotaxin, eotaxin-2, RANTES, and MCP-2, 3, 4) enhance the frequency of IL-4 producing basophils (p < 0.01), following Ag activation, and eotaxin lowers the Ag concentration responsible for IL-4 production by 40 fold (p < 0.01). These data demonstrate that after antigen activation, basophils are the predominant peripheral blood cells expressing IL-4 and IL-13, and add weight to the conclusions that basophils are envolved in the regulation of allergic diseases. Finally, our results describe a novel role for CC chemokine: the potentialisation of IL-4 expression, suggesting potential inovative approaches to treat allergic asthma.