title: Natural killer cell education does not affect the magnitude of granzyme B delivery to target cells by antibody-dependent cellular cytotoxicity.
abstract: OBJECTIVE
  Interest in the role of antibody-dependent cellular cytotoxicity (ADCC) in protection from HIV infection has grown since analyses of the RV144 HIV vaccine trial results found ADCC correlated with protection. Natural killer (NK) cells are among the effector cells that mediate ADCC. The level of antibody-induced NK cell activation depends on NK cell education through inhibitory NK cell receptor human leukocyte antigen (HLA) ligand interactions. Here, we investigated the impact of NK cell education on the delivery of Granzyme B (GzB) to target cells.
  
  
  METHODS
  Lymphocytes from 50 HIV-uninfected [30 Bw4 (Bw4) and 20 Bw4 (Bw6)] KIR3DL1 homozygote persons were used as effectors and cocultured with gp120-coated target cells in the presence of a single source of anti-HIV gp120 antibody to ascertain whether NK cell education status influenced the level of GzB delivered to target cells.
  
  
  METHODS
  The GTL assay assessed the frequency of GzB-positive (%GzB) CEM.NKr.CCR5 target cells generated by effectors from each individual. The frequency of CD107a, interferon (IFN)-γ and CCL4 NK cells was assessed as a measure of antibody-induced NK cell activation.
  
  
  RESULTS
  KIR3DL1 NK cells from the Bw4 group were more functional than KIR3DL1 NK cells. Despite this, the %GzB target cells generated in the GTL assay did not differ according to the KIR3DL1-HLA-B genotype of the effector cells. The %GzB cells positively correlated with the frequency of CD16KIR3DL1 NK cells in the effector population.
  
  
  CONCLUSIONS
  ADCC potency does not depend on NK cell education.
authors.affiliation: aResearch Institute of the McGill University Health Centre (RI-MUHC) bDivision of Experimental Medicine, McGill University, Montreal, Quebec, Canada cDepartment of Microbiology and Immunology at the Peter Doherty Institute, University of Melbourne, Melbourne, Victoria, Australia. dCentre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM) eMcGill AIDS Center, Lady Davis Institute, Jewish General Hospital, McGill University fDepartment of Family Medicine, Université de Montréal gChronic Viral Illness Service hDivision of Clinical Immunology, McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Gamze
authors.initials: G
authors.lastname: Isitman
authors.forename: Irene
authors.initials: I
authors.lastname: Lisovsky
authors.forename: Alexandra
authors.initials: A
authors.lastname: Tremblay-McLean
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Parsons
authors.forename: Naglaa H
authors.initials: NH
authors.lastname: Shoukry
authors.forename: Mark A
authors.initials: MA
authors.lastname: Wainberg
authors.forename: Julie
authors.initials: J
authors.lastname: Bruneau
authors.forename: Nicole F
authors.initials: NF
authors.lastname: Bernard
mesh_terms: D000920:Antibody-Dependent Cell Cytotoxicity; D002478:Cells, Cultured; D054407:Chemokine CCL4 / Q000032:analysis; D053804:Granzymes / Q000378:metabolism*; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000032:analysis; D007694:Killer Cells, Natural / Q000276:immunology*; D052118:Lysosomal-Associated Membrane Protein 1 / Q000032:analysis
chemical_list: C066507:CCL4 protein, human; D054407:Chemokine CCL4; D015483:HIV Antibodies; D052118:Lysosomal-Associated Membrane Protein 1; D007371:Interferon-gamma; D053804:Granzymes