Allergen exposure–induced differences in CD34+cell phenotype: relationship to eosinophilopoietic responses in different compartments

We hypothesized that the allergen-induced increased number of airway eosinophils results from increased recruitment of eosinophils from bone marrow (BM) and local development of CD34+cells into eosinophils. We also assumed that the phenotype of airway eosinophils depends on whether these cells have differentiated within BM or airway. C57BL/6 mice were sensitized and subsequently exposed to ovalbumin (OVA) on 5 consecutive days. Newly produced cells were labeled with a thymidine analog. Clonogenic activity and interleukin 5 (IL-5) release from bronchoalveolar lavage fluid (BALf) CD34+cells were evaluated by using cell-culture techniques. Allergen exposure induces increase in CD135+primitive myeloid progenitors within the BM CD34+cell population, without significant changes in total number of CD34+cells or newly produced CD34+cells. CD34+/IL-5Rα+cells in the first stage of cell differentiation were found only in BM, arguing that early commitment of CD34+cells into the eosinophil lineage is restricted to the BM compartment. Allergen exposure induces a shift in differentiation of BM, blood, and BALf eosinophillineage–committed CD34+cells toward mature eosinophils and recruitment of these cells via blood into airway. We further demonstrate in vitro that ability to multiply persists in BALf CD34+cells but not CD34–cells, likely via autocrine IL-5 release and IL-5–induced up-regulation of IL-5Rα.