Cutting Edge: Invariant V 14 NKT Cells Are Required for Allergen-Induced Airway Inflammation and Hyperreactivity in an Experimental Asthma Model (original) (raw)

2003, The Journal of Immunology

Airway hyperreactivity (AHR), eosinophilic inflammation with a Th2-type cytokine profile, and specific Th2mediated IgE production characterize allergic asthma. In this paper, we show that OVA-immunized J␣18 ؊/؊ mice, which are exclusively deficient in the invariant V␣14 ؉ (iV␣14), CD1d-restricted NKT cells, exhibit impaired AHR and airway eosinophilia, decreased IL-4 and IL-5 production in bronchoalveolar lavage fluid, and reduced OVA-specific IgE compared with wild-type (WT) littermates. Adoptive transfer of WT iV␣14 NKT cells fully reconstitutes the capacity of J␣18 ؊/؊ mice to develop allergic asthma. Also, specific tetramer staining shows that OVA-immunized WT mice have activated (CD69 ؉) iV␣14 NKT cells. Importantly, anti-CD1d mAb treatment blocked the ability of iV␣14 T cells to amplify eosinophil recruitment to airways, and both Th2 cytokine and IgE production following OVA challenge. In conclusion, these findings clearly demonstrate that iV␣14 NKT cells are required to participate in allergen-induced Th2 airway inflammation through a CD1d-dependent mechanism.