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

: Veres TZ, Kopcsanyi T, van Panhuys N, Gerner MY, Liu ZD, Rantakari P, Dunkel J, Miyasaka M, Salmi M, Jalkanen S, Germain RN

Publisher: AMER ASSOC IMMUNOLOGISTS

: 2017

: Journal of Immunology

: JOURNAL OF IMMUNOLOGY

: J IMMUNOL

: 198

: 2

: 895

: 907

: 13

: 0022-1767

: 1550-6606

DOI: https://doi.org/10.4049/jimmunol.1601448

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.