Myeloid dendritic cells induce Th2 responses to inhaled antigen, leading to eosinophilic airway inflammation

The aim of this study was to investigate whether dendritic cells (DCs) can induce sensitization to aeroallergen in a mouse model of allergic asthma. O valbumin-pulsed (OVA-pulsed) or unpulsed myeloid DCs that were injected int o the airways of naive mice migrated into the mediastinal lymph nodes. When challenged 2 weeks later with an aerosol of OVA, activated CD4 and CD8 lym phocytes, eosinophils, and neutrophils were recruited to the lungs of activ ely immunized mice. These CD4(+) lymphocytes produced predominantly IL-4 an d IL-5 but also IFN-gamma, whereas CD8(+) lymphocytes produced predominantl y IFN-gamma. Histological analysis revealed perivascular and peribronchial eosinophilic infiltrates and goblet cell hyperplasia. Studies in IL-4(-/-) and CD28(-/-) mice revealed that production of IL-4 by host cells and provi sion of costimulation to T cells by DCs were critical for inducing the resp onse. Lung CD4(+) T cells strongly expressed the Th2 marker T1/ST2, and sig naling through this molecule via a ligand expressed on DCs was essential fo r the establishment of airway eosinophilia. These data demonstrate that DCs in the airways induce sensitization to inhaled antigen and that molecules expressed on the surface of these cells are critical for the development of Th2-dependent airway eosinophilia.