Defective killing of dendritic cells by autologous natural killer cells from acute myeloid leukemia patients.
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.
Fauriat
Cyril
C
Service d'Hématologie (Pr G Sébahoun), Hôpital Nord, Chemin des Bourrelly, 13915 Marseille CEDEX 20, France.
Moretta
Alessandro
A
Olive
Daniel
D
Costello
Régis T
RT
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
D000951:Antigens, Neoplasm; C112260:NCR1 protein, human; D055627:Natural Cytotoxicity Triggering Receptor 1; D011971:Receptors, Immunologic