Dendritic cell and T cell responses in children with food allergy

Food allergy (FA) and eosinophilic oesophagitis (EE) are increasingly common clinical problems. Dendritic cells (DCs) are key regulators of the sensitization and effector phases of allergic immune responses, but their role in these diseases is largely unknown.Objective To evaluate for alterations in the phenotype and function of DCs in children with IgE-mediated milk allergy or EE compared with their non-affected siblings.Methods Plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) were prepared from peripheral blood of children with milk allergy (FA), EE, and non-affected siblings (CON). Purified pDCs and mDCs were cultured alone or with autologous CD4⁺ lymphocytes. Cytokine levels in plasma, or culture supernatants following stimulation, were measured using multiplex array immunoassay. Cell-surface molecule expression was determined by flow cytometry.Results DCs from FA subjects produced greater levels of pro-inflammatory cytokines (IL-6, TNF-α), granulocyte macrophage-colony forming factor, and mDC-derived IL-10 compared with controls following allergen exposure. T_H2 but not T_H1 cytokines were spontaneously produced in DC-CD4⁺ T cell co-cultures from children with FA and were not significantly increased after stimulation with milk extract, suggesting an ongoing activation in vivo. This hypothesis was further supported by evidence for elevated IL-5 and IL-13 protein in the plasma of children with both FA and EE. The only significant DC phenotypic differences were: (1) reduced levels of CD80 in EE subjects and (2) Fc RI expression that correlated with serum IgE levels in both groups of subjects.Conclusion This study suggests that DCs from children with FA and EE produce more pro-inflammatory cytokines, and that their CD4⁺ T cells are spontaneously activated to produce T_H2 cytokines in the presence of Fc RI-bearing DCs.