title: Human NK cells at early stages of differentiation produce CXCL8 and express CD161 molecule that functions as an activating receptor.
abstract: Human natural killer (NK) cell development is a step-by-step process characterized by phenotypically identified stages. CD161 is a marker informative of the NK cell lineage commitment, whereas CD56, CD117, and CD94/NKG2A contribute to define discrete differentiation stages. In cells undergoing in vitro differentiation from CD34(+) umbilical cord blood (UCB) progenitors, LFA-1 expression allowed to discriminate between immature noncytolytic CD161(+)CD56(+)LFA-1(-) and more differentiated cytolytic CD161(+)CD56(+)LFA-1(+) NK cells. CD161(+)CD56(+)LFA-1(-) NK cells produce large amounts of CXCL8 after phorbol myristate acetate (PMA) or cytokine treatment. Remarkably, CXCL8 mRNA expression was also detected in fresh stage III immature NK cells isolated from tonsils and these cells expressed CXCL8 protein on PMA stimulation. Within in vitro UCB-derived CD161(+)CD56(+)LFA-1(-) NK cells, CXCL8 release was also induced on antibody-mediated cross-linking of NKp44 and CD161. Such unexpected activating function of CD161 was confined to the CD161(+)CD56(+)LFA-1(-) subset, because it did not induce cytokine release or CD107a expression in CD161(+)CD56(+)LFA-1(+) cells or in mature peripheral blood NK cells. Anti-CXCL8 neutralizing antibody induced a partial inhibition of NK cell differentiation, which suggests a regulatory role of CXCL8 during early NK cell differentiation. Altogether, these data provide novel information that may offer clues to optimize NK cell maturation in hematopoietic stem cell transplantation.
authors.affiliation: Department of Experimental Medicine, University of Genova, Genoa, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Montaldo
authors.forename: Chiara
authors.initials: C
authors.lastname: Vitale
authors.forename: Francesca
authors.initials: F
authors.lastname: Cottalasso
authors.forename: Romana
authors.initials: R
authors.lastname: Conte
authors.forename: Timor
authors.initials: T
authors.lastname: Glatzer
authors.forename: Paolo
authors.initials: P
authors.lastname: Ambrosini
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moretta
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Mingari
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation; D002470:Cell Survival; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005312:Fetal Blood / Q000166:cytology / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000166:cytology* / Q000378:metabolism*; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000911:Antibodies, Monoclonal; C508606:CXCL8 protein, human; D016207:Cytokines; D016209:Interleukin-8; C527203:KLRB1 protein, human; D055651:NK Cell Lectin-Like Receptor Subfamily B; D012333:RNA, Messenger