title: Functional characterization of natural killer cells in type I leukocyte adhesion deficiency.
abstract: In this study, we analyzed IL-2-activated polyclonal natural killer (NK) cells derived from 2 patients affected by leukocyte adhesion deficiency type I (LAD1), an immunodeficiency characterized by mutations of the gene coding for CD18, the beta subunit shared by major leukocyte integrins. We show that LAD1 NK cells express normal levels of various triggering NK receptors (and coreceptors) and that mAb-mediated engagement of these receptors results in the enhancement of both NK cytolytic activity and cytokine production. Moreover, these activating NK receptors were capable of recognizing their specific ligands on target cells. Thus, LAD1 NK cells, similarly to normal NK cells, were capable of killing most human tumor cells analyzed and produced high amounts of IFN-gamma when cocultured in presence of target cells. Murine target cells represented a common exception, as they were poorly susceptible to LAD1 NK cells. Finally, LAD1 NK cells could efficiently kill or induce maturation of monocyte-derived immature dendritic cells (DCs). Altogether our present study indicates that in LAD1 patients, 3 important functions of NK cells (eg, cytotoxicity, IFN-gamma production, and DC editing) are only marginally affected and provides new insight on the cooperation between activating receptors and LFA-1 in the induction of NK cell activation and function.
authors.affiliation: Dipartimento di Medicina Sperimentale, Istituto Giannina Gaslini, University of Genoa, Largo G. Gaslini 5, 16147 Genoa, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Castriconi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Dondero
authors.forename: Claudia
authors.initials: C
authors.lastname: Cantoni
authors.forename: Mariella
authors.initials: M
authors.lastname: Della Chiesa
authors.forename: Carola
authors.initials: C
authors.lastname: Prato
authors.forename: Marina
authors.initials: M
authors.lastname: Nanni
authors.forename: Maurilia
authors.initials: M
authors.lastname: Fiorini
authors.forename: Lucia
authors.initials: L
authors.lastname: Notarangelo
authors.forename: Silvia
authors.initials: S
authors.lastname: Parolini
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moretta
authors.forename: Luigi
authors.initials: L
authors.lastname: Notarangelo
authors.forename: Alessandro
authors.initials: A
authors.lastname: Moretta
authors.forename: Cristina
authors.initials: C
authors.lastname: Bottino
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D018821:CD18 Antigens / Q000096:biosynthesis; D002448:Cell Adhesion; D002675:Child, Preschool; D003713:Dendritic Cells / Q000166:cytology; D006801:Humans; D007223:Infant; D007376:Interleukin-2 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology* / Q000378:metabolism; D007960:Leukocyte Disorders / Q000097:blood*; D007962:Leukocytes / Q000166:cytology*; D008024:Ligands; D008297:Male; D051379:Mice
chemical_list: D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D007376:Interleukin-2; D008024:Ligands