Antigen-specific cytotoxic T lymphocytes target airway CD103+ and CD11b+ dendritic cells to suppress allergic inflammation

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Nature Publishing Group
Allergic airway inflammation is driven by the recognition of inhaled allergen by T helper type 2 (Th2) cells in the airway and lung. Allergen-specific cytotoxic T lymphocytes (CTLs) can strongly reduce airway inflammation, however, the mechanism of their inhibitory activity is not fully defined. We used mouse models to show that allergen-specific CTLs reduced early cytokine production by Th2 cells in lung, and their subsequent accumulation and production of interleukin (IL)-4 and IL-13. In addition, treatment with specific CTLs also increased the proportion of caspase+ dendritic cells (DCs) in mediastinal lymph node (MLN), and decreased the numbers of CD103+ and CD11b+ DCs in the lung. This decrease required expression of the cytotoxic mediator perforin in CTLs and of the appropriate MHC-antigen ligand on DCs, suggesting that direct CTL-DC contact was necessary. Lastly, lung imaging experiments revealed that in airway-challenged mice XCR1-GFP+ DCs, corresponding to the CD103+ DC subset, and XCR1-GFP− CD11c+ cells, which include CD11b+ DCs and alveolar macrophages, both clustered in the areas surrounding the small airways and were closely associated with allergen-specific CTLs. Thus, allergen-specific CTLs reduce allergic airway inflammation by depleting CD103+ and CD11b+ DC populations in the lung, and may constitute a mechanism through which allergic immune responses are regulated.
Immunology, Dendritic cells, Flow cytometry, RNA, Cytotoxicity, CTL, T lymphocytes, CD103+, CD11b+, antigen, antibody
Mucosal Immunology, 2016, 9 pp. 229 - 239 (11)