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
H. Kayaba et al., 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, J IMMUNOL, 167(2), 2001, pp. 995-1003
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.