title: Multifunctional human CD56 low CD16 low natural killer cells are the prominent subset in bone marrow of both healthy pediatric donors and leukemic patients.
abstract: We phenotypically and functionally characterized a distinct CD56(low) natural killer cell subset based on CD16 expression levels in bone marrow and peripheral blood of healthy children and pediatric patients with acute lymphoblastic leukemia. Our findings demonstrate for the first time that CD56(low)CD16(low) natural killer cells are more abundant in bone marrow than in peripheral blood and that their frequency is further increased in children with acute lymphoblastic leukemia. Bone marrow and peripheral blood CD56(low)CD16(low) natural killer cells compared with CD56(low)CD16(high) natural killer cells express lower levels of killer inhibitory receptors, higher levels of CD27, CD127, CD122, CD25, but undetectable levels of CD57, suggesting that they have a higher proliferative and differentiation potential. Moreover, CD56(low)CD16(low) natural killer cells display higher levels of CXCR4 and undetectable levels of CX3CR1 and can be consistently and rapidly mobilized in peripheral blood in response to CXCR4 antagonist. Unlike CD56(low)CD16(high), both bone marrow and peripheral blood CD56(low)CD16(low) natural killer cells release IFNγ following cytokine stimulation, and represent the major cytotoxic natural killer cell population against K562 or acute lymphoblastic leukemia target cells. All these data suggest that CD56(low)CD16(low) natural killer cells are multifunctional cells, and that the presence of hematologic malignancies affects their frequency and functional ability at both tumor site and in the periphery.
authors.affiliation: Department Molecular Medicine, University of Rome "La Sapienza"
authors.forename: Helena
authors.initials: H
authors.lastname: Stabile
authors.affiliation: Department Molecular Medicine, University of Rome "La Sapienza"
authors.forename: Paolo
authors.initials: P
authors.lastname: Nisti
authors.affiliation: Department Experimental Medicine, University of Rome "La Sapienza"
authors.forename: Stefania
authors.initials: S
authors.lastname: Morrone
authors.affiliation: Department Pediatric Hematology/Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale Pediatrico Bambino Gesù, Rome and University of Pavia.
authors.forename: Daria
authors.initials: D
authors.lastname: Pagliara
authors.affiliation: Department Pediatric Hematology/Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale Pediatrico Bambino Gesù, Rome and University of Pavia.
authors.forename: Alice
authors.initials: A
authors.lastname: Bertaina
authors.affiliation: Department Pediatric Hematology/Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale Pediatrico Bambino Gesù, Rome and University of Pavia.
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.affiliation: Department Molecular Medicine, University of Rome "La Sapienza" Italian Institute of Technology, Genova, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Santoni
authors.affiliation: Department Molecular Medicine, University of Rome "La Sapienza" Eleonora Lorillard Spencer Cenci Foundation, Rome angela.gismondi@uniroma1.it.
authors.forename: Angela
authors.initials: A
authors.lastname: Gismondi
mesh_terms: D000328:Adult; D000367:Age Factors; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism*; D019002:CD56 Antigen / Q000378:metabolism*; D016022:Case-Control Studies; D015550:Cell Degranulation / Q000276:immunology; D018925:Chemokines / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003602:Cytotoxicity, Immunologic; D006801:Humans; D016130:Immunophenotyping; D007372:Interferons / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D007938:Leukemia / Q000276:immunology / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D010641:Phenotype; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism*
chemical_list: D019002:CD56 Antigen; D018925:Chemokines; D019038:Platelet Glycoprotein GPIb-IX Complex; D017452:Receptors, IgG; C094990:adhesion receptor; D007372:Interferons