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A CD8α(-) subpopulation of macaque circulatory natural killer cells can mediate both antibody-dependent and antibody-independent cytotoxic activities.

Abstract

Natural killer (NK) cells are important components of the innate immune system that mediate effector and regulatory functions. As effector cells, NK cells help control virus-infected cells through cell-mediated antibody-dependent mechanisms such as antibody-dependent cellular cytotoxicity (ADCC). Although macaques are an important and reliable animal model for the study of retrovirus-induced human diseases, and despite the crucial role played by NK cells in innate and adaptive immune responses against simian immunodeficiency virus (SIV), only a few studies have attempted to characterize different macaque NK cell subpopulations. In the present study, we identified a subpopulation of circulatory CD8α(-) macaque NK cells that express NK lineage markers and exhibit cytotoxic potential. CD8α(-) NK cells were phenotypically characterized as CD3(-) CD14(-) CD20(-) CD8α(-) cells that express NK cell markers including CD16, CD56, granzyme B, perforin, NKG2D and KIR2D. Based on their CD56/CD16 expression patterns, cells within the CD8α(-) gate can be divided into four subpopulations: CD56(dim) CD16(bright) , CD56(dim) CD16(-) , CD56(bright) CD16(-) , and CD56(-) CD16(-) cells. In contrast, CD8α(+) NK cells are 95% CD56(dim) CD16(bright) , which correlates with their high cytotoxic potential. Upon interleukin-15 activation, CD8α(-) cells up-regulated CD69 expression and produced low levels of interferon-γ and tumour necrosis factor-α. Sorted CD8α(-) NK cells were capable of killing MHC-I-devoid target cells and mediated ADCC responses against SIV gp120-coated target cells in the presence of macaque anti-gp120 antibodies. Taking into account CD8α(-) myeloid dendritic cells, we show that about 35% of macaque CD8α(-) cells represent a novel, functional population of circulatory NK cells that possesses cytotoxic potential and is capable of mediating anti-viral immune responses.

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  • Authors+Show Affiliations

    ,

    Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-5065, USA.

    ,

    Source

    Immunology 134:3 2011 Nov pg 326-40

    MeSH

    Animals
    Antibody-Dependent Cell Cytotoxicity
    CD56 Antigen
    CD8 Antigens
    Cells, Cultured
    Cytotoxicity, Immunologic
    Flow Cytometry
    Granzymes
    Interferon-gamma
    Interleukin-12
    Interleukin-15
    Killer Cells, Natural
    Leukocytes, Mononuclear
    Macaca mulatta
    Membrane Glycoproteins
    Perforin
    Receptors, IgG
    Reverse Transcriptase Polymerase Chain Reaction
    Simian Acquired Immunodeficiency Syndrome
    Tumor Necrosis Factor-alpha
    Viral Envelope Proteins

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Intramural

    Language

    eng

    PubMed ID

    21978002

    Citation

    Vargas-Inchaustegui, Diego A., et al. "A CD8α(-) Subpopulation of Macaque Circulatory Natural Killer Cells Can Mediate Both Antibody-dependent and Antibody-independent Cytotoxic Activities." Immunology, vol. 134, no. 3, 2011, pp. 326-40.
    Vargas-Inchaustegui DA, Demberg T, Robert-Guroff M. A CD8α(-) subpopulation of macaque circulatory natural killer cells can mediate both antibody-dependent and antibody-independent cytotoxic activities. Immunology. 2011;134(3):326-40.
    Vargas-Inchaustegui, D. A., Demberg, T., & Robert-Guroff, M. (2011). A CD8α(-) subpopulation of macaque circulatory natural killer cells can mediate both antibody-dependent and antibody-independent cytotoxic activities. Immunology, 134(3), pp. 326-40. doi:10.1111/j.1365-2567.2011.03493.x.
    Vargas-Inchaustegui DA, Demberg T, Robert-Guroff M. A CD8α(-) Subpopulation of Macaque Circulatory Natural Killer Cells Can Mediate Both Antibody-dependent and Antibody-independent Cytotoxic Activities. Immunology. 2011;134(3):326-40. PubMed PMID: 21978002.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - A CD8α(-) subpopulation of macaque circulatory natural killer cells can mediate both antibody-dependent and antibody-independent cytotoxic activities. AU - Vargas-Inchaustegui,Diego A, AU - Demberg,Thorsten, AU - Robert-Guroff,Marjorie, PY - 2011/10/8/entrez PY - 2011/10/8/pubmed PY - 2011/12/14/medline SP - 326 EP - 40 JF - Immunology JO - Immunology VL - 134 IS - 3 N2 - Natural killer (NK) cells are important components of the innate immune system that mediate effector and regulatory functions. As effector cells, NK cells help control virus-infected cells through cell-mediated antibody-dependent mechanisms such as antibody-dependent cellular cytotoxicity (ADCC). Although macaques are an important and reliable animal model for the study of retrovirus-induced human diseases, and despite the crucial role played by NK cells in innate and adaptive immune responses against simian immunodeficiency virus (SIV), only a few studies have attempted to characterize different macaque NK cell subpopulations. In the present study, we identified a subpopulation of circulatory CD8α(-) macaque NK cells that express NK lineage markers and exhibit cytotoxic potential. CD8α(-) NK cells were phenotypically characterized as CD3(-) CD14(-) CD20(-) CD8α(-) cells that express NK cell markers including CD16, CD56, granzyme B, perforin, NKG2D and KIR2D. Based on their CD56/CD16 expression patterns, cells within the CD8α(-) gate can be divided into four subpopulations: CD56(dim) CD16(bright) , CD56(dim) CD16(-) , CD56(bright) CD16(-) , and CD56(-) CD16(-) cells. In contrast, CD8α(+) NK cells are 95% CD56(dim) CD16(bright) , which correlates with their high cytotoxic potential. Upon interleukin-15 activation, CD8α(-) cells up-regulated CD69 expression and produced low levels of interferon-γ and tumour necrosis factor-α. Sorted CD8α(-) NK cells were capable of killing MHC-I-devoid target cells and mediated ADCC responses against SIV gp120-coated target cells in the presence of macaque anti-gp120 antibodies. Taking into account CD8α(-) myeloid dendritic cells, we show that about 35% of macaque CD8α(-) cells represent a novel, functional population of circulatory NK cells that possesses cytotoxic potential and is capable of mediating anti-viral immune responses. SN - 1365-2567 UR - https://www.unboundmedicine.com/medline/citation/21978002/A_CD8α_____subpopulation_of_macaque_circulatory_natural_killer_cells_can_mediate_both_antibody_dependent_and_antibody_independent_cytotoxic_activities_ L2 - https://doi.org/10.1111/j.1365-2567.2011.03493.x DB - PRIME DP - Unbound Medicine ER -