title: 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.
authors: Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-5065, USA.
authors: Diego A
authors: DA
authors: Vargas-Inchaustegui
authors: Thorsten
authors: T
authors: Demberg
authors: Marjorie
authors: M
authors: Robert-Guroff
mesh_terms: D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects / Q000276:immunology*; D019002:CD56 Antigen / Q000276:immunology / Q000378:metabolism; D016827:CD8 Antigens / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology*; D005434:Flow Cytometry; D053804:Granzymes / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018664:Interleukin-12 / Q000494:pharmacology; D019409:Interleukin-15 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008253:Macaca mulatta; D008562:Membrane Glycoproteins / Q000276:immunology; D054353:Perforin / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D017452:Receptors, IgG / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016097:Simian Acquired Immunodeficiency Syndrome / Q000097:blood / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000276:immunology
chemical_list: D019002:CD56 Antigen; D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain; D019409:Interleukin-15; D008562:Membrane Glycoproteins; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; D014759:Viral Envelope Proteins; C069623:gp120 protein, Simian immunodeficiency virus; D054353:Perforin; D018664:Interleukin-12; D007371:Interferon-gamma; D053804:Granzymes