title: NK cell function and antibodies mediating ADCC in HIV-1-infected viremic and controller patients.
abstract: Natural killer (NK) cells have been suggested to play a protective role in HIV disease progression. One potent effector mechanism of NK cells is antibody-dependent cellular cytotoxicity (ADCC) mediated by antiviral antibodies binding to the FcγRIIIa receptor (CD16) on NK cells. We investigated NK cell-mediated ADCC function and the presence of ADCC antibodies in plasma from 20 HIV-1-infected patients and 10 healthy donors. The HIV-positive patients were divided into two groups: six who controlled viremia for at least 8 y without treatment (controllers), and 14 who were persistently viremic and not currently on treatment. Plasma from both patient groups induced NK cell IFN-γ expression and degranulation in response to HIV-1 envelope (Env) gp140-protein-coated cells. Patient antibodies mediating ADCC were largely directed towards the Env V3 loop, as identified by a gp140 protein lacking the V3 loop. Interestingly, in two controllers ADCC-mediating antibodies were more broadly directed to other parts of Env. A high viral load in patients correlated with decreased ADCC-mediated cytolysis of gp140-protein-coated target cells. NK cells from both infected patients and healthy donors degranulated efficiently in the presence of antibody-coated HIV-1-infected Jurkat cells. In conclusion, the character of ADCC-mediating antibodies differed in some controllers compared to viremic patients. NK cell ADCC activity is not compromised in HIV-infected patients.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology and Strategic Research Center IRIS, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Susanne E
authors.initials: SE
authors.lastname: Johansson
authors.forename: Erik
authors.initials: E
authors.lastname: Rollman
authors.forename: Amy W
authors.initials: AW
authors.lastname: Chung
authors.forename: Rob J
authors.initials: RJ
authors.lastname: Center
authors.forename: Bo
authors.initials: B
authors.lastname: Hejdeman
authors.forename: Ivan
authors.initials: I
authors.lastname: Stratov
authors.forename: Jorma
authors.initials: J
authors.lastname: Hinkula
authors.forename: Britta
authors.initials: B
authors.lastname: Wahren
authors.forename: Klas
authors.initials: K
authors.lastname: Kärre
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kent
authors.forename: Louise
authors.initials: L
authors.lastname: Berg
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology*; D005260:Female; D015483:HIV Antibodies / Q000097:blood / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology / Q000502:physiology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology; D019562:Viral Load; D014766:Viremia / Q000276:immunology* / Q000821:virology; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D007074:Immunoglobulin G; D010446:Peptide Fragments; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1