Perturbations of natural killer cell regulatory functions in respiratory allergic diseases

Background: Allergic diseases are characterized by abnormal responses to allergens favored by an inappropriate regulation of the TH1-TH2 polarization. Natural killer (NK) cells give rise to a complex NK/dendritic cell (DC) cross-talk that would help TH1 responses. Objective: By analyzing peripheral blood NK cells from 12 patients with either allergic rhinitis or rhinitis and intermittent asthma, we evaluated whether these cells were impaired in their ability to interact with DCs. Methods: Different circulating NK cell subsets were analyzed by flow cytofluorimetry. Mixed NK/DC cultures were performed to assess the reciprocal functional interactions. NK cells were analyzed for their ability to induce DC maturation and cytokine production, and to kill immature DCs. In addition, DCs were assessed for their ability to induce cytokine production by NK cells. Results: We first analyzed the CD56++CD16+/- cells, a subset of circulating NK cells that is able to respond to DCs by proliferating and producing IFN-γ. Our analysis revealed that this NK cell subpopulation was significantly reduced in most patients. This was reflected by reduced NK cell-mediated IFN-γ production in response to DCs. Also, the capability of promoting DC maturation and/or killing immature DCs, a function sustained by CD56+CD16+ NK cells, was reduced in most patients. Conclusions: We suggest that allergic diseases are accompanied by a partial impairment of the NK cell capability of promoting and maintaining appropriate TH1 responses. © 2008 American Academy of Allergy, Asthma & Immunology.