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 cy totoxicity reactions toward the parasite Schistosoma mansoni in vitro. Howe ver, because receptor expression is low on these cells, its functional role is still controversial. In this study, we have measured surface and intrac ellular expression of FC epsilon RI by blood eosinophils from hypereosinoph ilic patients and normal donors. The number of unoccupied receptors corresp onded to similar to4,500 Ab binding sites per cell, whereas 50,000 Ab bindi ng sites per cell were detected intracellularly. Eosinophils from patients displayed significantly more unoccupied receptors than cells from normal do nors. This number correlated to both serum IgE concentrations and to membra ne-bound IgE. The lack of Fc,ERI expression by mouse eosinophils has hamper ed further studies. To overcome this fact and experimentally, confirm our f indings on human eosinophils, we engineered IL-5 x hFc epsilon RI alpha dou ble-transgenic mice, whose bone marrow, blood, spleen, and peritoneal eosin ophils expressed Fc epsilon RI levels similar to levels of human eosinophil s, after 4 days culture with IgE in the presence of IL-5. Both human and mo use eosinophils were able to secrete IL-10 upon Fc epsilon RI engagement. T hus, comparative analysis of cells from patients and from a relevant animal model allowed us to clearly demonstrate that Fc epsilon RI-mediated eosino phil activation leads to IL-10 secretion. Through Fc epsilon RI expression, these cells are able to contribute to both the regulation of the immune re sponse and to its effector mechanisms.