title: Natural killer cell deficiency in patients with non-Hodgkin lymphoma after lung transplantation.
abstract: BACKGROUND
  Post-transplant non-Hodgkin lymphoma (NHL) is a well-recognized complication of solid-organ transplantation, and pharmacologic suppression of adaptive immunity plays a major role in its development. However, the role of natural killer (NK) cells in post-lung transplant de novo NHL is unknown.
  
  
  METHODS
  Extensive phenotypic analyses of NK cells from patients diagnosed with NHL after liver or lung transplantation were conducted with multicolor flow cytometry. Polyfunctionality assays simultaneously assessed NK cell degranulation (CD107a) and intracellular cytokine production (interferon-γ and tumor necrosis factor-α) in the presence of NHL target cells.
  
  
  RESULTS
  The development of de novo NHL is linked to NK-cell maturation defects, including overexpression of NKG2A and CD62L and down-modulation of inhibitory killer immunoglobulin-like receptors and CD57 receptors. More importantly, in patients who developed NHL after lung transplantation, we observed a specific down-modulation of the activating receptors (NKp30, NKp46, and NKG2D) and a sharp decrease in perforin expression and degranulation against NHL target cells.
  
  
  CONCLUSIONS
  Our results suggest that accumulation of abnormal NK cells could play a role in the outgrowth of NHL after lung transplantation, independently of the immunosuppressive regimen.
authors.affiliation: Sorbone Universités, University Pierre et Marie Curie, Univ Paris 06, CR7, Centre d'Immunologie et des Maladies Infectieuses-Paris, Paris, France; Institut National de la Recherche Médicale, U1135, Centre d'Immunologie et des Maladies Infectieuses-Paris, Paris, France; Centre National de la Recherche Scientifique, ERL 8255, Centre d'Immunologie et des Maladies Infectieuses-Paris, Paris, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Baychelier
authors.affiliation: Sorbone Universités, University Pierre et Marie Curie, Univ Paris 06, CR7, Centre d'Immunologie et des Maladies Infectieuses-Paris, Paris, France; Institut National de la Recherche Médicale, U1135, Centre d'Immunologie et des Maladies Infectieuses-Paris, Paris, France; Centre National de la Recherche Scientifique, ERL 8255, Centre d'Immunologie et des Maladies Infectieuses-Paris, Paris, France.
authors.forename: Abla
authors.initials: A
authors.lastname: Achour
authors.affiliation: Sorbone Universités, University Pierre et Marie Curie, Univ Paris 06, CR7, Centre d'Immunologie et des Maladies Infectieuses-Paris, Paris, France; Institut National de la Recherche Médicale, U1135, Centre d'Immunologie et des Maladies Infectieuses-Paris, Paris, France; Centre National de la Recherche Scientifique, ERL 8255, Centre d'Immunologie et des Maladies Infectieuses-Paris, Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital La Pitié-Salpêtrière, Service Hématologie Clinique, Paris, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Nguyen
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Départementd'Hématologie et d'Immunologie, Le Kremlin-Bicêtre, Paris, France; Univ Paris-Sud, UFR Médecine, Le Kremlin-Bicêtre, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Raphael
authors.affiliation: Institut National de la Recherche Médicale, UMR-S1160, Paris, France; Univ Paris Diderot, Sorbonne Paris Cité, Institut Université d'Hématologie, Paris, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Toubert
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Service d'Hématologie, Le Kremlin-Bicêtre, Paris, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Besson
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Unité de Recherche Clinique, Le Kremlin-Bicêtre, Paris, France.
authors.forename: Armelle
authors.initials: A
authors.lastname: Arnoux
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital La Pitié-Salpêtrière, Service Hématologie Clinique, Paris, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Roos-Weil
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Centre des Innovations Thérapeutiques en Oncologie et Hématologie, Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Marty
authors.affiliation: Hôpital Foch, Service de Chirurgie Thoracique et de Transplantation Pulmonaire, Suresnes, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Chapelier
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Paul Brousse, Centre Hépatobiliaire, Villejuif, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Samuel
authors.affiliation: Sorbone Universités, University Pierre et Marie Curie, Univ Paris 06, CR7, Centre d'Immunologie et des Maladies Infectieuses-Paris, Paris, France; Institut National de la Recherche Médicale, U1135, Centre d'Immunologie et des Maladies Infectieuses-Paris, Paris, France; Centre National de la Recherche Scientifique, ERL 8255, Centre d'Immunologie et des Maladies Infectieuses-Paris, Paris, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Debré
authors.affiliation: Sorbone Universités, University Pierre et Marie Curie, Univ Paris 06, CR7, Centre d'Immunologie et des Maladies Infectieuses-Paris, Paris, France; Institut National de la Recherche Médicale, U1135, Centre d'Immunologie et des Maladies Infectieuses-Paris, Paris, France; Centre National de la Recherche Scientifique, ERL 8255, Centre d'Immunologie et des Maladies Infectieuses-Paris, Paris, France. Electronic address: vincent.vieillard@upmc.fr.
authors.forename: Vincent
authors.initials: V
authors.lastname: Vieillard
mesh_terms: D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D016040:Lung Transplantation; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000276:immunology*
keywords: Lung transplantation; NK cells; natural killer cells; non-Hodgkin lymphoma; perforin