title: CD56brightCD16- killer Ig-like receptor- NK cells display longer telomeres and acquire features of CD56dim NK cells upon activation.
abstract: Human NK cells can be divided into CD56(dim)CD16(+) killer Ig-like receptors (KIR)(+/-) and CD56(bright)CD16(-) KIR(-) subsets that have been characterized extensively regarding their different functions, phenotype, and tissue localization. Nonetheless, the developmental relationship between these two NK cell subsets remains controversial. We report that, upon cytokine activation, peripheral blood (PB)-CD56(bright) NK cells mainly gain the signature of CD56(dim) NK cells. Remarkably, KIR can be induced not only on CD56(bright), but also on CD56(dim) KIR(-) NK cells, and their expression correlates with lower proliferative response. In addition, we demonstrate for the first time that PB-CD56(dim) display shorter telomeres than PB- and lymph node (LN)-derived CD56(bright) NK cells. Along this line, although human NK cells collected from nonreactive LN display almost no KIR and CD16 expression, NK cells derived from highly reactive LN, efferent lymph, and PB express significant amounts of KIR and CD16, implying that CD56(bright) NK cells could acquire these molecules in the LN during inflammation and then circulate through the efferent lymph into PB as KIR(+)CD16(+) NK cells. Altogether, our results suggest that CD56(bright)CD16(-) KIR(-) and CD56(dim)CD16(+)KIR(+/-) NK cells correspond to sequential steps of differentiation and support the hypothesis that secondary lymphoid organs can be sites of NK cell final maturation and self-tolerance acquisition during immune reaction.
authors.affiliation: Department of Clinical Immunology, German Rheumatism Research Centre, Deutsches Rheuma-Forschungszentrum Berlin, Berlin, Germany.
authors.forename: Chiara
authors.initials: C
authors.lastname: Romagnani
authors.forename: Kerstin
authors.initials: K
authors.lastname: Juelke
authors.forename: Michela
authors.initials: M
authors.lastname: Falco
authors.forename: Barbara
authors.initials: B
authors.lastname: Morandi
authors.forename: Antonella
authors.initials: A
authors.lastname: D'Agostino
authors.forename: Roberta
authors.initials: R
authors.lastname: Costa
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ratto
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Forte
authors.forename: Paolo
authors.initials: P
authors.lastname: Carrega
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Lui
authors.forename: Romana
authors.initials: R
authors.lastname: Conte
authors.forename: Till
authors.initials: T
authors.lastname: Strowig
authors.forename: Alessandro
authors.initials: A
authors.lastname: Moretta
authors.forename: Christian
authors.initials: C
authors.lastname: Münz
authors.forename: Andreas
authors.initials: A
authors.lastname: Thiel
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moretta
authors.forename: Guido
authors.initials: G
authors.lastname: Ferlazzo
mesh_terms: D019002:CD56 Antigen / Q000032:analysis*; D002478:Cells, Cultured; D006801:Humans; D006965:Hyperplasia; D018664:Interleukin-12 / Q000494:pharmacology; D019409:Interleukin-15 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D017452:Receptors, IgG / Q000032:analysis*; D011971:Receptors, Immunologic / Q000032:analysis*; D054340:Receptors, KIR; D017634:Self Tolerance; D016615:Telomere
chemical_list: D019002:CD56 Antigen; D019409:Interleukin-15; D007376:Interleukin-2; D017452:Receptors, IgG; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D018664:Interleukin-12