Intratracheal priming with ovalbumin- and ovalbumin 323-339 peptide-pulseddendritic cells induces airway hyperresponsiveness, lung eosinophilia, goblet cell hyperplasia, and inflammation

Dendritic cells (DC) are the primary APC responsible for the capture of all ergens in the airways and the shuttling of processed allergens to the drain ing lymph nodes where Ag presentation and T cell activation take place. The mechanism of this Ag handling and presentation in asthma is poorly underst ood. In addition, the feasibility of asthma induction by DC priming has not been directly tested. In this report an asthma model using intratracheally (i.t.) injected splenic DC was used to address these issues. DC pulsed wit h a model Ag OVA or the major MHC class II-restricted OVA T epitope peptide OVA(323-339) and instilled i.t. primed mice to exhibit asthma-like disease s. With OVA as the Ag, mice exhibit airway hyperresponsiveness (AHR), lung eosinophilia and inflammation, and pulmonary goblet cell hyperplasia. In OV A(323-339)-immunized mice, AHR and goblet cell hyperplasia were noted, with little eosinophilia and parenchymal inflammation. The latter finding provi des evidence for dissociating AHR from eosinophilia. In both cases mediasti nal node hypertrophy occurred, and high levels of Th2 cytokines were produc ed by the lung and mediastinal lymph node cells (LNC). Interestingly, media stinal LNC also produced high levels of Th1 cytokines. Lung cells produced much less Th1 cytokines than these LNC. These results demonstrate that DC w hen introduced i.t. are potent in inducing asthma-like diseases by recruiti ng lymphocytes to the lung-draining lymph nodes and by stimulating Th2 resp onses and also suggest that the lung environment strongly biases T cell res ponses to Th2.