title: CD27 engagement by a soluble CD70 protein enhances non-cytolytic antiviral activity of CD56bright natural killer cells by IFN-γ secretion.
abstract: We investigated regulation of human NK cell function by CD27 engagement using a recombinant soluble CD70 protein. CD27 was preferentially expressed on CD56(bright) NK cells, and soluble CD70 protein bound to CD27(+)CD56(bright) NK cells. While soluble CD70 protein enhanced IFN-γ secretion by CD56(bright) NK cells in the presence of IL-12, it augmented neither cytolytic activity nor proliferation of NK cells. Thus, we next asked if soluble CD70 protein could be used to induce non-cytolytic antiviral activity of NK cells using an in vitro hepatitis C virus (HCV) infection system. Soluble CD70 protein stimulated NK cells to suppress HCV replication by enhancing NK cell IFN-γ secretion without killing infected cells. Taken together, we demonstrate that CD27 engagement by a soluble CD70 protein enhances non-cytolytic antiviral activity of CD56(bright) NK cells by IFN-γ secretion. Thus, this soluble CD70 protein may be useful for the treatment of viral infections such as HCV infection.
authors.affiliation: Department of Biological Sciences, KAIST, Daejeon 305-701, Republic of Korea; Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon 305-701, Republic of Korea.
authors.forename: Young-Soon
authors.initials: YS
authors.lastname: Jang
authors.forename: Wonseok
authors.initials: W
authors.lastname: Kang
authors.forename: Dong-Yeop
authors.initials: DY
authors.lastname: Chang
authors.forename: Pil Soo
authors.initials: PS
authors.lastname: Sung
authors.forename: Bum-Chan
authors.initials: BC
authors.lastname: Park
authors.forename: Seok Ho
authors.initials: SH
authors.lastname: Yoo
authors.forename: Young Woo
authors.initials: YW
authors.lastname: Park
authors.forename: Eui-Cheol
authors.initials: EC
authors.lastname: Shin
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D053282:CD27 Ligand / Q000494:pharmacology*; D019002:CD56 Antigen / Q000235:genetics / Q000276:immunology*; D015870:Gene Expression; D016174:Hepacivirus / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism*; D018664:Interleukin-12 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D061251:Primary Cell Culture; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction; D012995:Solubility; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000235:genetics / Q000276:immunology*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D053282:CD27 Ligand; D019002:CD56 Antigen; C505771:CD70 protein, human; C522918:NCAM1 protein, human; D011994:Recombinant Proteins; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D018664:Interleukin-12; D007371:Interferon-gamma
keywords: CD27; CD70; Hepatitis C virus; IFN-γ; Natural killer cells