title: Impact of Graft-Versus-Graft Natural Killer Cell Alloreactivity on Single Unit Dominance After Double Umbilical Cord Blood Transplantation.
abstract: Natural killer (NK) cell alloreactivity is favored after double umbilical cord blood transplantation (dUCBT) in which cord blood (UCB) units and patients are often HLA class I mismatched. Generally, only 1 UCB unit persists after dUCBT. We hypothesize, that NK cell alloreactivity mediated by killer cell immunoglobulin-like receptor (KIR)-HLA interactions may explain the dominance of 1UCB unit over the other after dUCBT.
  
  
  
  We investigated the impact of KIR NK cell alloreactivities on the dominance of 1 full UCB unit in 50 dUCBT. We analyzed the effects of the KIR/HLA genetic incompatibilities and studied cord blood cells at both the phenotypic and functional levels.
  
  
  
  The genetic combination of KIR3DL1 loser UCB unit/Bw4 winner UCB unit determined both the dominance of 1 UCB unit (hazards ratio, 2.88 [1.32-6.27], P = 0.0077) and correlated with an increased incidence of relapse (hazards ratio, 4.91 [1.39-17.3], P = 0.0134). It is interesting to note that cord blood cells exhibited extremely low HLA class I expression. Moreover, resting cord blood KIR3DL1 NK cells exhibited a basal alloreactivity against Bw4 target cells that increased upon activation, thus triggering death by apoptosis.
  
  
  
  Our unicentric study suggests, for the first time, the significant impact of KIR NK cell alloreactivity in the determination of which UCB unit will dominate in dUCBT.
authors: 1 Etablissement Français du Sang, Université de Nantes, Immunovirologie et Polymorphisme Génétique, Nantes, France. 2 Plateforme de Biométrie, Direction de la Recherche, CHU Nantes, France. 3 Service d'Hématologie Clinique, CHU Hotel Dieu, Nantes, France. 4 Laboratoire d'Hématologie Biologique, CHU Hotel Dieu, Nantes, France. 5 Hôpital Mère-Enfant, CHU Hotel Dieu, Nantes, France. 6 Laboratoire d'Histocompatibilité et d'Immunogénétique, EFS Nantes, France. 7 LabEx Transplantex, Université de Strasbourg, France. 8 Inserm UMR 892, Nantes, France. 9 Division of Hematology and Bone Marrow Transplantation, City of Hope, National Medical Center, Duarte, CA.
authors: Pauline
authors: P
authors: Rettman
authors: Catherine
authors: C
authors: Willem
authors: Christelle
authors: C
authors: Volteau
authors: Nolwenn
authors: N
authors: Legrand
authors: Patrice
authors: P
authors: Chevallier
authors: Laurence
authors: L
authors: Lodé
authors: Julie
authors: J
authors: Esbelin
authors: Anne
authors: A
authors: Cesbron
authors: Marc
authors: M
authors: Bonneville
authors: Philippe
authors: P
authors: Moreau
authors: David
authors: D
authors: Senitzer
authors: Christelle
authors: C
authors: Retière
authors: Katia
authors: K
authors: Gagne
mesh_terms: D017209:Apoptosis; D002478:Cells, Cultured; D036101:Cord Blood Stem Cell Transplantation / Q000009:adverse effects*; D003602:Cytotoxicity, Immunologic; D005602:France; D005838:Genotype; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology*; D006648:Histocompatibility; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D010641:Phenotype; D054341:Receptors, KIR3DL1 / Q000235:genetics / Q000276:immunology*; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D006680:HLA Antigens; C515083:KIR3DL1 protein, human; D054341:Receptors, KIR3DL1