Perturbations of natural killer cell regulatory functions in respiratory allergic diseases

Francesca Scordamaglia, MDa, Mirna Balsamo, PhDd, Antonio Scordamaglia, MDa, Alessandro Moretta, MDbc, Maria Cristina Mingari, PhDbe, Giorgio Walter Canonica, MDa, Lorenzo Moretta, MDbcd, Massimo Vitale, PhDe

Author address: 

a Clinica Malattie dell'Apparato Respiratorio e Allergologia, Dipartimento di Medicina Interna, Universití  di Genova, Genoa, Italy b Dipartimento di Medicina Sperimentale, Universití  di Genova, Genoa, Italy c Centro di Eccellenza per la Ricerca

Abstract: 

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 cellmediated 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. Key words: NK cells, allergy, DC, NK1/NK2, TH1/TH2 cytokines, rhinitis, asthma Abbreviations used: DC, Dendritic cell, FACS, Fluorescence-activated cell sorting, iDC, Immature dendritic cell, KIR, Killer immunoglobulin-like receptors, LN, Lymph node, Mo-DC, Monocyte-derived dendritic cell, NK, Natural killer, PBL, Peripheral blood lymphocyte, SPT, Skin prick test, TLR, Toll-like receptor
2008

abstract No: 

page 479-485

Full conference title: 

2008 American Academy of Allergy, Asthma, and Immunology Annual Meeting
    • AAAAI 2008 (64th)