title: Expression of activating receptors on natural killer cells from AIDS-related lymphoma patients.
abstract: BACKGROUND
  Abnormal NK phenotype and cytotoxic functions have been described in acute myeloid leukemia, chronic lymphocytic leukemia, myeloma and myelodysplastic syndromes. Defective NK cytotoxicity is due to decreased expression of the Natural Cytotoxicity Receptors (NCRs), 2B4/CD244/p38, or NKG2D. This prompted us to test the expression of these molecules on circulating NK cells from patients with AIDS-related lymphomas (RL) in comparison with HIV + patients without lymphoma, healthy subjects and HIV-negative patients with lymphoma.
  
  
  METHODS
  Blood samples were analyzed by flow cytometry for NCRs, 2B4/CD244/p38 and NKG2D expression on NK cells defined as CD3-/CD56+ lymphocytes. We also analyzed by quantitative PCR specific RNA for NKp30/NCR3 and NKp46/NCR1.
  
  
  RESULTS
  We could not detect any defect in NKp46/NCR1 expression between all groups. NKp44/NCR2, NKp30/NCR3 and NKG2D had lower expression in AIDS-RL in comparison with HIV + patients without lymphoma when compared to patients with similar (>0.3 G/L) CD4+ lymphocyte levels. Expression of 2B4/CD244/p38 was lower in AIDS-RL than in HIV-negative lymphoma. Comparison of specific NKp30/NCR3 and NKp46/NCR1 RNA showed increased steady state levels, despite decreased surface expression for NKp30/NCR3, suggesting abnormal post-transcriptional regulatory mechanisms.
  
  
  CONCLUSIONS
  We show a more pronounced defect in NK activating molecule when HIV infection is associated with lymphoma than when only one condition (HIV positivity or lymphoma) is present. Defective NK phenotype, in addition to CD4+ depletion and dysfunction, may participate to the increased incidence of lymphoma in HIV patients.
authors.affiliation: Université Aix-Marseille, Hôpital Nord, Laboratoire d'Hématologie, Chemin des Bourrely, 13915 Marseille Cedex 20, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Mercier-Bataille
authors.affiliation: Université Aix-Marseille, Hôpital Nord, Laboratoire d'Hématologie, Chemin des Bourrely, 13915 Marseille Cedex 20, France ; Technologies Avancées pour la Génomique et la Clinique (TAGC)/unité INSERM U1090, route de Luminy, 13008 Marseille, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Sanchez
authors.affiliation: Technologies Avancées pour la Génomique et la Clinique (TAGC)/unité INSERM U1090, route de Luminy, 13008 Marseille, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Baier
authors.affiliation: Université Aix-Marseille, Hôpital Nord, Laboratoire d'Hématologie, Chemin des Bourrely, 13915 Marseille Cedex 20, France.
authors.forename: Thérèse
authors.initials: T
authors.lastname: Le Treut
authors.affiliation: Service d'Oncologie-Hématologie, CHU de Nice, Hôpital Larchet, 151 Rte Saint Antoine Ginestiere, BP 7906202 Nice Cedex 3, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Mounier
authors.affiliation: Université Aix-Marseille, Hôpital Nord, Service des maladies infectieuses, Chemin des Bourrely, 13915 Marseille Cedex 20, France.
authors.forename: Saadia
authors.initials: S
authors.lastname: Mokhtari
authors.affiliation: Laboratoire d'immunologie des tumeurs, Institut Paoli-Calmette, bd Leï Roure, 13008 Marseille, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Olive
authors.affiliation: Université Aix-Marseille, Faculté de La Timone, Unité d'Aide Méthodologique, 27 Boulevard Jean Moulin, 13005 Marseille, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Baumstarck
authors.affiliation: Université Aix-Marseille, Hôpital Nord, Laboratoire d'Hématologie, Chemin des Bourrely, 13915 Marseille Cedex 20, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Sébahoun
authors.affiliation: Service d'hématologie et immunologie clinique, CHU Bicêtre, 78 rue du Gal Leclerc, 94275 Le Kremlin-Bicêtre, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Besson
authors.affiliation: Technologies Avancées pour la Génomique et la Clinique (TAGC)/unité INSERM U1090, route de Luminy, 13008 Marseille, France ; Université Aix-Marseille, Hôpital La Conception, Service d'Hématologie et Thérapie Cellulaire, 147 Boulevard Baille, 13005 Marseille, France.
authors.forename: Régis T
authors.initials: RT
authors.lastname: Costello
keywords: Antitumor immune response; HIV-1; Lymphoma; Natural cytotoxicity receptors; Natural killer cells