Natural killer cells determine development of allergen-induced eosinophilic airway inflammation in mice

The earliest contact between antigen and the innate immune system is though t to direct the subsequent antigen-specific T cell response. We hypothesize d that cells of the innate immune system, such as natural killer (NK) cells , NK1.1(+) T cells (NKT cells), and gamma/delta T cells, may regulate the d evelopment of allergic airway disease. We demonstrate here that depletion o f NK1.1(+) cells (NK cells and NKT cells) before immunization inhibits pulm onary eosinophil and CD3(+) T cell infiltration as well as increased levels of interleukin (IL)-4, IL-5, and IL-12 in bronchoalveolar lavage fluid in a murine model of allergic asthma. Moreover, systemic allergen-specific imm unoglobulin (Ig)E and IgG2a levels and the number of IL-4 and interferon ga mma-producing splenic cells were diminished in mice depleted of NK1.1(+) ce lls before the priming regime. Depletion of NK1.1(+) cells during the chall enge period only did not influence pulmonary eosinophilic inflammation. CD1 d1 mutant mice, deficient in NKT cells but with normal NK cells, developed lung tissue eosinophilia and allergen-specific IgE levels not different fro m those observed in wild-type mice. Mice deficient in gamma/delta T cells s howed a mild attenuation of lung tissue eosinophilia in this model. Taken t ogether, these findings suggest a critical role of NK cells, but not of NKT cells, for the development of allergen-induced airway inflammation, and th at this effect of NK cells is exerted during die immunization. If translata ble to humans, these data suggest that NK cells may be critically important for deciding whether allergic eosinophilic airway disease will develop. Th ese observations are also compatible with a pathogenic role for the increas ed NK cell activity observed in human asthma.