title: Human cytomegalovirus-induced NKG2C(hi) CD57(hi) natural killer cells are effectors dependent on humoral antiviral immunity.
abstract: Recent studies indicate that expansion of NKG2C-positive natural killer (NK) cells is associated with human cytomegalovirus (HCMV); however, their activity in response to HCMV-infected cells remains unclear. We show that NKG2C(hi) CD57(hi) NK cells gated on CD3(neg) CD56(dim) cells can be phenotypically identified as HCMV-induced NK cells that can be activated by HCMV-infected cells. Using HCMV-infected autologous macrophages as targets, we were able to show that these NKG2C(hi) CD57(hi) NK cells are highly responsive to HCMV-infected macrophages only in the presence of HCMV-specific antibodies, whereas they are functionally poor effectors of natural cytotoxicity. We further demonstrate that NKG2C(hi) CD57(hi) NK cells are intrinsically responsive to signaling through CD16 cross-linking. Our findings show that the activity of pathogen-induced innate immune cells can be enhanced by adaptive humoral immunity. Understanding the activity of NKG2C(hi) CD57(hi) NK cells against HCMV-infected cells will be of relevance for the further development of adoptive immunotherapy.
authors: Institute of Virology, University Medical Center Ulm, Ulm, Germany.
authors: Zeguang
authors: Z
authors: Wu
authors: Christian
authors: C
authors: Sinzger
authors: Giada
authors: G
authors: Frascaroli
authors: Johanna
authors: J
authors: Reichel
authors: Carina
authors: C
authors: Bayer
authors: Li
authors: L
authors: Wang
authors: Reinhold
authors: R
authors: Schirmbeck
authors: Thomas
authors: T
authors: Mertens
mesh_terms: D000914:Antibodies, Viral / Q000276:immunology; D018959:CD57 Antigens / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D003587:Cytomegalovirus / Q000276:immunology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D058851:GPI-Linked Proteins / Q000276:immunology; D006801:Humans; D056724:Immunity, Humoral / Q000276:immunology*; D016219:Immunotherapy, Adoptive / Q000379:methods; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000821:virology; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000276:immunology / Q000378:metabolism*; D009500:Neutralization Tests; D017452:Receptors, IgG / Q000276:immunology; D018709:Statistics, Nonparametric
chemical_list: D000914:Antibodies, Viral; D018959:CD57 Antigens; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; C527059:KLRC2 protein, human; D055654:NK Cell Lectin-Like Receptor Subfamily C; D017452:Receptors, IgG
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