Plasmacytoid dendritic cells (PDCs) accumulate in the nasal mucosa of allergic rhinitis patients, but their function in upper airway allergy has not been determined. CpG oligodeoxynucleotides, potent adjuvants in immunotherapeutic strategies in animal models, are especially effective at activating PDCs. These cells are therefore potential targets for immunomodulation in humans.

In this study, PDCs were compared with CD11c⁺ dendritic cells (DCs), a very potent antigen-presenting cell type, for their capacity to induce allergen-dependent activation of T_H2 memory cells. Then, we investigated whether CpG-activated PDCs were able to modulate the allergen-specific T_H2 memory response.

DCs were isolated from patients with upper airway allergy and cocultured with autologous CD4⁺ T cells with or without grass pollen extract and CpG. In some experiments cells were restimulated with allergen-pulsed monocyte-derived DCs. T-cell activation was measured by their proliferative response and cytokine production.

PDCs stimulated allergen-dependent T-cell proliferation and T_H2 cytokine production as efficiently as CD11c⁺ DCs. CpG-activated PDCs inhibited allergen-dependent proliferation of T_H2 memory cells and markedly increased IFN-γ production in PDC/T-cell cocultures; the former effect depended on the CpG-induced IFN-⍺/β production by the PDCs.

Our results demonstrated that PDCs efficiently drive allergen-dependent T_H2 memory responses, suggesting that they play an active role in the allergic reaction. However, in the presence of CpG, PDCs were responsible for increased production of the T_H1-related cytokines IFN-⍺ and IFN-γ, indicating that mucosal PDCs may be targets for CpG-based immunotherapeutic strategies against airway allergy.