title: Characterization of CD56-/CD16+ natural killer (NK) cells: a highly dysfunctional NK subset expanded in HIV-infected viremic individuals.
abstract: Natural killer (NK) cells are an important component of the innate immune response against viral infections. NK cell-mediated cytolytic activity is defective in HIV-infected individuals with high levels of viral replication. In the present study, we examined the phenotypic and functional characteristics of an unusual CD56(-)/CD16(+) (CD56(-)) NK subset that is greatly expanded in HIV-viremic individuals. The higher level of expression of inhibitory NK receptors and the lower level of expression of natural cytotoxicity receptors observed in the CD56(-) NK fraction compared with that of CD56(+) NK cells was associated with extremely poor in vitro cytotoxic function of this subset. In addition, the secretion of certain cytokines known to be important in initiating antiviral immune responses was markedly reduced in the CD56(-), as compared with the CD56(+) NK cell subset. These data suggest that the expansion of this highly dysfunctional CD56(-) NK cell subset in HIV-viremic individuals largely accounts for the impaired function of the total NK cell population.
authors.affiliation: Laboratory of Immunoregulation and Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. dmavilio@niaid.nih.gov
authors.forename: Domenico
authors.initials: D
authors.lastname: Mavilio
authors.forename: Gabriella
authors.initials: G
authors.lastname: Lombardo
authors.forename: Janet
authors.initials: J
authors.lastname: Benjamin
authors.forename: Diana
authors.initials: D
authors.lastname: Kim
authors.forename: Dean
authors.initials: D
authors.lastname: Follman
authors.forename: Emanuela
authors.initials: E
authors.lastname: Marcenaro
authors.forename: M Angeline
authors.initials: MA
authors.lastname: O'Shea
authors.forename: Audrey
authors.initials: A
authors.lastname: Kinter
authors.forename: Colin
authors.initials: C
authors.lastname: Kovacs
authors.forename: Alessandro
authors.initials: A
authors.lastname: Moretta
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Fauci
mesh_terms: D019002:CD56 Antigen / Q000032:analysis*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D017452:Receptors, IgG / Q000032:analysis*; D011971:Receptors, Immunologic / Q000032:analysis; D055607:Receptors, Natural Killer Cell; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014766:Viremia / Q000276:immunology*
chemical_list: D019002:CD56 Antigen; D007376:Interleukin-2; D017452:Receptors, IgG; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor