title: CD2-CD58 interactions are pivotal for the activation and function of adaptive natural killer cells in human cytomegalovirus infection.
abstract: The existence and expansion of adaptive NK-cell subsets have been linked to HCMV infection. Phenotypically, a majority of adaptive NK cells expresses the activating receptor NKG2C and CD57. Some of the molecular factors driving the expansion of NKG2C+CD57+NK cells in HCMV infection have been identified. The direct interaction of adaptive NK cells with HCMV-infected cells, preceding the expansion, however, remains less studied. Recently, adaptive NK cells were reported to express higher levels of the co-activating receptor CD2. We explored whether CD2 was directly involved in the response of adaptive NK cells to HCMV. In a co-culture system of human PBMCs and productively infected fibroblasts, we observed an upregulation of CD69, CD25, and HLA-DR on all NK cells. However, only in adaptive NK cells was this increase largely blocked by antibodies against CD2 and CD58. Functionally, this blockade also resulted in diminished production of IFN-γ and TNF-α by adaptive human NK cells in response to HCMV-infected cells. Our results demonstrate that binding of CD2 to upregulated CD58 on infected cells is a critical event for antibody-mediated activation and subsequent effector functions of adaptive NKG2C+CD57+NK cells during the antiviral response.
authors.affiliation: Clinical Cooperation Unit Applied Tumor Immunity, Antigen Presentation & T/NK Cell Activation Group, German Cancer Research Center (DKFZ/D121), Heidelberg, Germany. a.roelle@dkfz.de.
authors.forename: Alexander
authors.initials: A
authors.lastname: Rölle
authors.affiliation: Institute of Virology, Medical Center, Albert-Ludwigs-University Freiburg, Freiburg, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Halenius
authors.affiliation: Innate Immunity Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Ewen
authors.affiliation: Innate Immunity Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Adelheid
authors.initials: A
authors.lastname: Cerwenka
authors.affiliation: Institute of Virology, Medical Center, Albert-Ludwigs-University Freiburg, Freiburg, Germany.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Hengel
authors.affiliation: Clinical Cooperation Unit Applied Tumor Immunity, Antigen Presentation & T/NK Cell Activation Group, German Cancer Research Center (DKFZ/D121), Heidelberg, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Momburg
mesh_terms: D056704:Adaptive Immunity; D000906:Antibodies / Q000378:metabolism; D018801:CD2 Antigens / Q000378:metabolism*; D018968:CD58 Antigens / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology*; D005347:Fibroblasts / Q000276:immunology* / Q000821:virology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D011485:Protein Binding; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000906:Antibodies; D018801:CD2 Antigens; D018968:CD58 Antigens; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma
keywords: ADCC; Adaptive NK cells; CD2; CD57; CD58; HCMV; Human cytomegalovirus; LFA-3; NKG2C
  