Natural Killer (NK) cells have been implicated in the development of allergic airway inflammation. However the in vivo role of NK cells has not been firmly established due to the lack of animal models with selective NK cell deficiencies. We studied the role of NK cells in a model of ovalbumin-induced allergic airway disease (OVA-AAD) using NK-deficient (NKD) mice, perforin-/- mice, and mice depleted of Ly49A/D/G+ NK cell subsets. Induction of OVA-AAD in wild-type (WT) mice resulted in the expansion of airway NK cells and the development of pronounced airway eosinophilia. In the absence of NK cells or specific NK cell subsets, either in NKD mice, or after depletion of Ly49A/D/G+ NK cells, the development of OVA-AAD was significantly impaired as seen by decreased airway inflammation, decreased secretion of IL-4, IL-5 and IL-13 and diminished OVA-specific antibody production. Furthermore, while OVA-exposure induced a dramatic expansion of dendritic cells in WT mice, their induction was significantly attenuated in NKD mice. Development of OVA-AAD in perforin-/- mice suggested that the proinflammatory role of NK cells is not dependent on perforin-mediated cytotoxicity. Lastly, induction of allergic disease by OVA-specific CD4 T cells from WT but not NK-depleted or NKD mice in RAG-/- recipients, demonstrates that NK cells are essential for T cell priming. In summary, our data demonstrate that NK cells play an important and distinct role in the development of AAD.

2014