title: New insights on the natural killer cell repertoire from a thorough analysis of cord blood cells.
abstract: Although CB NK cells are characterized as immature lymphocytes, their impressive expansion and efficient graft-versus-leukemia response have been highlighted early after UCBT. To better evaluate their potential as source of effective NK cells, we revisited the study of NK cell repertoire from a large cohort of CB samples. Our study showed that the CB NK cell repertoire appears to be constructed early, depending on KIR gene content, but not on the autologous HLA environment. NKG2A was expressed on a large proportion of CB NK cells that inversely correlated with KIR(+) NK cell frequency. Self-HLA class I molecule-educated CB KIR(+) NK cells present a lower spontaneous lysis than do their adult counterparts, which is probably related to the low expression of activating NK receptors. We describe for the first time a proliferative and cytotoxic NKG2C(+) NK cell subset representing more than 10% of CB NK cells. NKG2A strongly inhibited CB NK cell degranulation, and its coexpression on NKG2C(+) NK cells may contribute to limiting their activation. Overall, the CB NK cell repertoire is constructed early and harbors numerous functional abilities shared by adult NK cells. In addition, their naïve viral status and fast expansion confer numerous advantages in immunotherapy on CB NK cells.
authors.affiliation: Immunovirologie et Polymorphisme Génétique, Etablissement Français du Sang, Université de Nantes, Nantes, France;
authors.forename: Pauline
authors.initials: P
authors.lastname: Rettman
authors.affiliation: Immunovirologie et Polymorphisme Génétique, Etablissement Français du Sang, Université de Nantes, Nantes, France;
authors.forename: Catherine
authors.initials: C
authors.lastname: Willem
authors.affiliation: Immunovirologie et Polymorphisme Génétique, Etablissement Français du Sang, Université de Nantes, Nantes, France;
authors.forename: Gaëlle
authors.initials: G
authors.lastname: David
authors.affiliation: Immunovirologie et Polymorphisme Génétique, Etablissement Français du Sang, Université de Nantes, Nantes, France;
authors.forename: Raphaëlle
authors.initials: R
authors.lastname: Riou
authors.affiliation: Immunovirologie et Polymorphisme Génétique, Etablissement Français du Sang, Université de Nantes, Nantes, France;
authors.forename: Nolwenn
authors.initials: N
authors.lastname: Legrand
authors.affiliation: Hôpital Mère-Enfant, Centre Hospitalier Universitaire Hotel Dieu, Nantes, France;
authors.forename: Julie
authors.initials: J
authors.lastname: Esbelin
authors.affiliation: Laboratoire d'Histocompatibilité et d'Immunogénétique, Etablissement Français du Sang, Université de Nantes, France; LabEx Transplantex, Université de Strasbourg, France; and.
authors.forename: Anne
authors.initials: A
authors.lastname: Cesbron
authors.affiliation: Division of Hematology and Bone Marrow Transplantation, City of Hope, National Medical Center, Duarte, CA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Senitzer
authors.affiliation: Immunovirologie et Polymorphisme Génétique, Etablissement Français du Sang, Université de Nantes, Nantes, France; Laboratoire d'Histocompatibilité et d'Immunogénétique, Etablissement Français du Sang, Université de Nantes, France; LabEx Transplantex, Université de Strasbourg, France; and.
authors.forename: Katia
authors.initials: K
authors.lastname: Gagne
authors.affiliation: Immunovirologie et Polymorphisme Génétique, Etablissement Français du Sang, Université de Nantes, Nantes, France;
authors.forename: Christelle
authors.initials: C
authors.lastname: Retière
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D005312:Fetal Blood / Q000276:immunology* / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D054340:Receptors, KIR / Q000378:metabolism*; D055607:Receptors, Natural Killer Cell / Q000378:metabolism*
chemical_list: D015395:Histocompatibility Antigens Class I; D054340:Receptors, KIR; D055607:Receptors, Natural Killer Cell
keywords: KIR; NK cells; NKG2C; differentiation