title: Antibody-mediated response of NKG2Cbright NK cells against human cytomegalovirus.
abstract: Human CMV (HCMV) infection promotes a variable and persistent expansion of functionally mature NKG2C(bright) NK cells. We analyzed NKG2C(bright) NK cell responses triggered by Abs from HCMV(+) sera against HCMV-infected MRC5 fibroblasts. Specific Abs promoted the degranulation (i.e., CD107a expression) and the production of cytokines (TNF-α and IFN-γ) by a significant fraction of NK cells, exceeding the low natural cytotoxicity against HCMV-infected targets. NK cell-mediated Ab-dependent cell-mediated cytotoxicity was limited by viral Ag availability and HLA class I expression on infected cells early postinfection and increased at late stages, overcoming viral immunoevasion strategies. Moreover, the presence of specific IgG triggered the activation of NK cells against Ab-opsonized cell-free HCMV virions. As compared with NKG2A(+) NK cells, a significant proportion of NKG2C(bright) NK cells was FcεR γ-chain defective and highly responsive to Ab-driven activation, being particularly efficient in the production of antiviral cytokines, mainly TNF-α. Remarkably, the expansion of NKG2C(bright) NK cells in HCMV(+) subjects was related to the overall magnitude of TNF-α and IFN-γ cytokine secretion upon Ab-dependent and -independent activation. We show the power and sensitivity of the anti-HCMV response resulting from the cooperation between specific Abs and the NKG2C(bright) NK-cell subset. Furthermore, we disclose the proinflammatory potential of NKG2C(bright) NK cells, a variable that could influence the individual responses to other pathogens and tumors.
authors: Universitat Pompeu Fabra, 08002 Barcelona, Spain;
authors: Marcel
authors: M
authors: Costa-Garcia
authors: Universitat Pompeu Fabra, 08002 Barcelona, Spain;
authors: Andrea
authors: A
authors: Vera
authors: Instituto de Investigación Sanitaria Puerta de Hierro, 28222 Majadahonda, Spain; and.
authors: Manuela
authors: M
authors: Moraru
authors: Instituto de Investigación Sanitaria Puerta de Hierro, 28222 Majadahonda, Spain; and.
authors: Carlos
authors: C
authors: Vilches
authors: Universitat Pompeu Fabra, 08002 Barcelona, Spain; Institut Hospital del Mar d'Investigacions Mèdiques, 08003 Barcelona, Spain.
authors: Miguel
authors: http://orcid.org/0000-0003-4882-065X
authors: M
authors: López-Botet
authors: Institut Hospital del Mar d'Investigacions Mèdiques, 08003 Barcelona, Spain amuntasell@imim.es miguel.lopez-botet@upf.edu.
authors: Aura
authors: http://orcid.org/0000-0003-2894-0486
authors: A
authors: Muntasell
mesh_terms: D000914:Antibodies, Viral / Q000276:immunology*; D000917:Antibody Formation / Q000276:immunology*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000276:immunology*; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism / Q000821:virology; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000276:immunology* / Q000378:metabolism; D017455:Receptors, IgE / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D014771:Virion / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D007074:Immunoglobulin G; C527059:KLRC2 protein, human; D055654:NK Cell Lectin-Like Receptor Subfamily C; D017455:Receptors, IgE; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma