title: Defective killing of dendritic cells by autologous natural killer cells from acute myeloid leukemia patients.
abstract: At the frontier between innate and adaptive immunity, dendritic cells (DCs) secrete numerous cytokines and express costimulatory molecules that initiate or enhance natural killer (NK) and T-lymphocyte responses. NK cells also regulate DC physiology by killing immature DCs (iDCs), thus limiting inflammation and inappropriate T-lymphocyte tolerization. In a previous study, we have reported that NK cells from acute myeloid leukemia patients (AML-NK cells) have deficient natural cytotoxicity receptor (NCR) expression. Herein, we analyzed the consequences of such a defect regarding the regulatory role of AML-NK cells in DC physiology. We show that NK cells display poor cytolytic capacities against DCs derived from healthy donor monocytes or derived from autologous leukemic blasts. These data point to a novel defect in the regulation of adaptive immune responses initiated by DCs in AML patients. This may lead to specific T-lymphocyte tolerization by spontaneous or ex vivo expanded iDCs expressing leukemia-derived antigens.
authors.affiliation: Service d'Hématologie (Pr G Sébahoun), Hôpital Nord, Chemin des Bourrelly, 13915 Marseille CEDEX 20, France.
authors.forename: Cyril
authors.initials: C
authors.lastname: Fauriat
authors.forename: Alessandro
authors.initials: A
authors.lastname: Moretta
authors.forename: Daniel
authors.initials: D
authors.lastname: Olive
authors.forename: Régis T
authors.initials: RT
authors.lastname: Costello
mesh_terms: D000208:Acute Disease; D017951:Antigen Presentation / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007111:Immunity, Cellular; D007694:Killer Cells, Natural / Q000276:immunology / Q000473:pathology*; D007951:Leukemia, Myeloid / Q000276:immunology*; D055627:Natural Cytotoxicity Triggering Receptor 1; D011971:Receptors, Immunologic / Q000172:deficiency; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; C112260:NCR1 protein, human; D055627:Natural Cytotoxicity Triggering Receptor 1; D011971:Receptors, Immunologic