Intratracheal Priming with Ovalbumin- and Ovalbumin 323-339 petide-Pulsed Dendritic Cells Induces Airway Hyperresponsiveness, Lung Eosinophilia, Goblet Cell Hyperplasia,and Inflammation

摘要

Dendritic cells (DC) are the primary A PC responsible for the capture of allergens in the airways and the shuttling of processed allergens to the draining lymph nodes where Ag presentation and T cell activation take place. The mechanism of this Ag handling and presentation in asthma is poorly understood. 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 with a model Ag OVA or the major MHC class lI-restricted OV AT epitope peptide OV A323-339 and instilled i.t. primed mice to exhibit asthma-Iike diseases. With OV A as the Ag, ~ce exhibit airway hyperresponsiveness (AHR), lung eosinophilia and inflammation, and pulmonary goblet cell hyperplasia. In OV A323-339-immunized mice, AHR and goblet cell hyperplasia were noted, with little eosinophilia and parenchymal inffammation. The latter finding provides evidence for dissociating AHR from eosinophilia. In both cases mediastinal node hypertrophy occurred, and high levels of Th2 cytokines were produced by the lung and mediastinal lymph node cells (LNC). Interestingly, mediastinal LNC also produced high levels of Th1 cytokines. Lung cells produced much less Th1 cytokines than these LNC. These results demonstrate that DC when introduced i.t. are potent in inducingI asthma-Iike diseases by ~ecruiting Iymphocy~es to the lung-draining lymph nodes and by stimulating Th2 responses and also I suggest that the lung environment strongly biases T cell responses to Th2.