title: Rapid degranulation of NK cells following activation by HIV-specific antibodies.
abstract: Ab-dependent cellular cytotoxicity (ADCC) Abs stimulate NK cell effector functions and play a role in protecting from and controlling viral infections. We characterized ADCC Abs in a cross-sectional cohort of 80 HIV-infected subjects not on antiretroviral therapy. We analyzed ADCC response by killing fluorescently labeled target cells, as well as expression of IFN-gamma and the degranulation marker CD107a from activated NK cells as measured by a novel intracellular cytokine assay. HIV-specific ADCC directed toward Envelope proteins were present in the majority of 80 untreated HIV-infected individuals measured by killing function. Similarly, most subjects had HIV-specific Abs that mediated degranulation or cytokine expression by NK cells. Interestingly, there was a poor correlation between ADCC-mediated killing of fluorescently labeled whole Envelope protein-pulsed cell lines and Ab-mediated expression of IFN-gamma by NK cells. However, in contrast to healthy donor NK cells, autologous patient NK cells more effectively degranulated granzyme B in response to ADCC activation. Activation of NK cells in response to stimulation by HIV-specific Abs occurs at least as rapidly as activation of Gag-specific CTLs. Our studies highlight the complexity of ab-mediated NK cell activation in HIV infection, and suggest new avenues toward studying the utility of ADCC in controlling HIV infection.
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Melbourne, Australia.
authors.forename: Amy W
authors.initials: AW
authors.lastname: Chung
authors.forename: Erik
authors.initials: E
authors.lastname: Rollman
authors.forename: Rob J
authors.initials: RJ
authors.lastname: Center
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kent
authors.forename: Ivan
authors.initials: I
authors.lastname: Stratov
mesh_terms: D000328:Adult; D000918:Antibody Specificity; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D015550:Cell Degranulation / Q000276:immunology*; D002461:Cell Line, Transformed; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis; D005452:Fluoresceins; D005456:Fluorescent Dyes; D015483:HIV Antibodies / Q000097:blood / Q000502:physiology*; D015488:HIV Antigens / Q000097:blood / Q000276:immunology; D015658:HIV Infections / Q000097:blood / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007424:Intracellular Fluid / Q000737:chemistry / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D008213:Lymphocyte Activation / Q000276:immunology*; D013388:Succinimides; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology
chemical_list: C087165:5-(6)-carboxyfluorescein diacetate succinimidyl ester; D016207:Cytokines; D005452:Fluoresceins; D005456:Fluorescent Dyes; D015483:HIV Antibodies; D015488:HIV Antigens; D013388:Succinimides; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1