Allergen-Induced CD4+ T Cell Cytokine Production within Airway Mucosal Dendritic Cell–T Cell Clusters Drives the Local Recruitment of Myeloid Effector Cells

Allergic asthma develops in the mucosal tissue of small bronchi. At these sites, local cytokine production by Th2/Th17 cells is believed to be critical for the development of tissue eosinophilia/neutrophilia. Using the mouse trachea as a relevant model of human small airways, we performed advanced in vivo dynamic and in situ static imaging to visualize individual cytokine-producing T cells in the airway mucosa and to define their immediate cellular environment. Upon allergen sensitization, newly recruited CD4+ T cells formed discrete Ag-driven clusters with dendritic cells (DCs). Within T cell–DC clusters, a small fraction of CD4+ T cells produced IL-13 or IL-17 following prolonged Ag-specific interactions with DCs. As a result of local Th2 cytokine signaling, eosinophils were recruited into these clusters. Neutrophils also infiltrated these clusters in a T cell–dependent manner, but their mucosal distribution was more diffuse. Our findings reveal the focal nature of allergen-driven responses in the airways and define multiple steps with potential for interference with the progression of asthmatic pathology.