Decreases in human dendritic cell-dependent T_H2-like responses after acute in vivo IgE neutralization

Background: Dendritic cells (DCs) and other professional antigen-presenting cells express a variant of the high-affinity IgE receptor known as αγ₂, which, on the basis of in vitro findings, has long been implicated to function in facilitating allergen uptake and presentation to T_H cells. Objectives: To use omalizumab as an in vivo tool to neutralize IgE binding to circulating dendritic cells and to assess whether this results in altered DC-dependent T-cell responsiveness to allergen ex vivo. Methods: Subjects with cat allergy were enrolled in a 3.5-month, double blind, randomized (3.5:1), placebo-controlled trial of omalizumab using standard dosing for allergic asthma. Blood plasmacytoid and myeloid DCs were assessed at baseline and posttreatment for expression of surface IgE, Fcε{lunate}RIα, and induction of CD4⁺T-cell proliferation and cytokine responses to cat allergen. Results: IgE expression on plasmacytoid and myeloid DCs from omalizumab-treated subjects (n = 12) decreased by ≥95% posttreatment (P = .0005), whereas Fcε{lunate}RIα expression decreased by 66% and 48%, respectively (P = .0005). Cat allergen-induced proliferation in DC/T-cell cocultures observed at baseline was suppressed ∼20% to 40% postomalizumab treatment (P = .001). Multiplexing for cytokines in plasmacytoid DC/T-cell cocultures also showed decreases in IL-5, IL-13, and IL-10 (P < .05), whereas IL-2 and IFN-γ were unaltered or slightly increased. These changes were not evident in placebo-control subjects (n = 4). Conclusion: IgE likely facilitates allergen presentation by dendritic cells in vivo and is also important in regulating DC-dependent T-cell cytokines during effector phases of allergic disease.