title: Natural killer cells in HIV-1 infection: dichotomous effects of viremia on inhibitory and activating receptors and their functional correlates.
abstract: Natural killer (NK) cells play a central role in host defense against various pathogens. Functional defects of NK cells in HIV-1 infection as a direct effect of abnormal expression or function of inhibitory NK receptors (iNKRs), activating natural cytotoxicity receptors (NCRs), and NKG2D have not yet been described. This study demonstrates an expansion of the functionally defective CD56-/CD16+ population of NK cells in viremic versus aviremic patients. We also demonstrate that in HIV-infected viremic patients, expression of iNKRs was well conserved and that in most cases, there was a trend toward increased expression on NK cells as compared with healthy donors. It was also demonstrated that the major activating NK receptors, with the exception of NKG2D, were significantly down-regulated. In contrast, the expression of iNKRs and activating receptors in HIV-infected individuals whose viremia was suppressed to below detectable levels by highly active antiretroviral therapy for 2 years or longer was comparable to that of healthy donors. Functional tests confirmed that the abnormal expression of the activating receptors and of iNKRs was associated with a markedly impaired NK cytolytic function. This phenomenon is not attributed to a direct HIV-1 infection of NK cells; thus, this study may provide insight into the mechanisms of impaired host defenses in HIV-1 viremic patients.
authors.affiliation: Laboratory of Immunoregulation, 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: Janet
authors.initials: J
authors.lastname: Benjamin
authors.forename: Marybeth
authors.initials: M
authors.lastname: Daucher
authors.forename: Gabriella
authors.initials: G
authors.lastname: Lombardo
authors.forename: Shyam
authors.initials: S
authors.lastname: Kottilil
authors.forename: Marie A
authors.initials: MA
authors.lastname: Planta
authors.forename: Emanuela
authors.initials: E
authors.lastname: Marcenaro
authors.forename: Cristina
authors.initials: C
authors.lastname: Bottino
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moretta
authors.forename: Alessandro
authors.initials: A
authors.lastname: Moretta
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Fauci
mesh_terms: D000911:Antibodies, Monoclonal / Q000378:metabolism; D019002:CD56 Antigen / Q000096:biosynthesis; D015536:Down-Regulation; D005434:Flow Cytometry; D015658:HIV Infections; D015497:HIV-1 / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000821:virology*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D010641:Phenotype; D016133:Polymerase Chain Reaction; D017452:Receptors, IgG / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D019002:CD56 Antigen; D017452:Receptors, IgG; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma