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 T(H)1-T(H)2 polarization. Natural killer (NK) cells give rise to a complex NK/dendritic cell (DC) cross-talk that would help T(H)1 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-gamma. Our analysis revealed that this NK cell subpopulation was significantly reduced in most patients. This was reflected by reduced NK cell-mediated IFN-gamma 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 T(H)1 responses.
Scordamaglia
Francesca
F
Clinica Malattie dell'Apparato Respiratorio e Allergologia, Dipartimento di Medicina Interna, Università di Genova, Genoa, Italy.
Balsamo
Mirna
M
Scordamaglia
Antonio
A
Moretta
Alessandro
A
Mingari
Maria Cristina
MC
Canonica
Giorgio Walter
GW
Moretta
Lorenzo
L
Vitale
Massimo
M
D000328:Adult; D019002:CD56 Antigen / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D016922:Cellular Senescence; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009000:Monocytes / Q000473:pathology; D017452:Receptors, IgG / Q000378:metabolism; D012130:Respiratory Hypersensitivity / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology*
D019002:CD56 Antigen; D017452:Receptors, IgG; D007371:Interferon-gamma