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PMID: 15699323 Published · ppublish English Journal Article

Characterization of CD56-/CD16+ natural killer (NK) cells: a highly dysfunctional NK subset expanded in HIV-infected viremic individuals.

Mavilio D, Lombardo G, Benjamin J, Kim D, Follman D, Marcenaro E, O'Shea MA, Kinter A, Kovacs C, Moretta A, Fauci AS

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.

MeSH Terms
CD56 Antigen/analysis Granulocyte-Macrophage Colony-Stimulating Factor/biosynthesis HIV Infections/immunology Humans Immunophenotyping Interferon-gamma/biosynthesis Interleukin-2/pharmacology Killer Cells, Natural/immunology Lymphocyte Activation Receptors, IgG/analysis Receptors, Immunologic/analysis Receptors, Natural Killer Cell Tumor Necrosis Factor-alpha/biosynthesis Viremia/immunology
Chemicals
CD56 Antigen Interleukin-2 Receptors, IgG Receptors, Immunologic Receptors, Natural Killer Cell Tumor Necrosis Factor-alpha Interferon-gamma Granulocyte-Macrophage Colony-Stimulating Factor
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Mavilio Domenico
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
Lombardo Gabriella
Benjamin Janet
Kim Diana
Follman Dean
Marcenaro Emanuela
O'Shea M Angeline
Kinter Audrey
Kovacs Colin
Moretta Alessandro
Fauci Anthony S
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
2005-02-22
Epub
2005-00-07
Pages
2886-91
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC549494
Subset
IM
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