Human eosinophils and human high affinity IgE receptor transgenic mouse eosinophils express low levels of high affinity IgE receptor, but release IL-10 upon receptor activation

Fc epsilon RI expressed by human eosinophils is involved in IgE-mediated cytotoxicity reactions toward the parasite Schistosoma mansoni in vitro. However, because receptor expression is low on these cells, its functional role is still controversial. In this study, we have measured surface and intracellular expression of FC epsilon RI by blood eosinophils from hypereosinophilic patients and normal donors. The number of unoccupied receptors corresponded to similar to4,500 Ab binding sites per cell, whereas 50,000 Ab binding sites per cell were detected intracellularly. Eosinophils from patients displayed significantly more unoccupied receptors than cells from normal donors. This number correlated to both serum IgE concentrations and to membrane-bound IgE. The lack of Fc,ERI expression by mouse eosinophils has hampered further studies. To overcome this fact and experimentally, confirm our findings on human eosinophils, we engineered IL-5 x hFc epsilon RI alpha double-transgenic mice, whose bone marrow, blood, spleen, and peritoneal eosinophils expressed Fc epsilon RI levels similar to levels of human eosinophils, after 4 days culture with IgE in the presence of IL-5. Both human and mouse eosinophils were able to secrete IL-10 upon Fc epsilon RI engagement. Thus, comparative analysis of cells from patients and from a relevant animal model allowed us to clearly demonstrate that Fc epsilon RI-mediated eosinophil activation leads to IL-10 secretion. Through Fc epsilon RI expression, these cells are able to contribute to both the regulation of the immune response and to its effector mechanisms.