title: CD94 surface density identifies a functional intermediary between the CD56bright and CD56dim human NK-cell subsets.
abstract: Human CD56(bright) natural killer (NK) cells possess little or no killer immunoglobulin-like receptors (KIRs), high interferon-gamma (IFN-gamma) production, but little cytotoxicity. CD56(dim) NK cells have high KIR expression, produce little IFN-gamma, yet display high cytotoxicity. We hypothesized that, if human NK maturation progresses from a CD56(bright) to a CD56(dim) phenotype, an intermediary NK cell must exist, which demonstrates more functional overlap than these 2 subsets, and we used CD94 expression to test our hypothesis. CD94(high)CD56(dim) NK cells express CD62L, CD2, and KIR at levels between CD56(bright) and CD94(low)CD56(dim) NK cells. CD94(high)CD56(dim) NK cells produce less monokine-induced IFN-gamma than CD56(bright) NK cells but much more than CD94(low)CD56(dim) NK cells because of differential interleukin-12-mediated STAT4 phosphorylation. CD94(high)CD56(dim) NK cells possess a higher level of granzyme B and perforin expression and CD94-mediated redirected killing than CD56(bright) NK cells but lower than CD94(low)CD56(dim) NK cells. Collectively, our data suggest that the density of CD94 surface expression on CD56(dim) NK cells identifies a functional and likely developmental intermediary between CD56(bright) and CD94(low)CD56(dim) NK cells. This supports the notion that, in vivo, human CD56(bright) NK cells progress through a continuum of differentiation that ends with a CD94(low)CD56(dim) phenotype.
authors.affiliation: Department of Molecular Virology, Immunology, and Medical Genetics, Ohio State University, Columbus, OH 43210, USA.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Yu
authors.forename: Hsiaoyin C
authors.initials: HC
authors.lastname: Mao
authors.forename: Min
authors.initials: M
authors.lastname: Wei
authors.forename: Tiffany
authors.initials: T
authors.lastname: Hughes
authors.forename: Jianying
authors.initials: J
authors.lastname: Zhang
authors.forename: Il-kyoo
authors.initials: IK
authors.lastname: Park
authors.forename: Shujun
authors.initials: S
authors.lastname: Liu
authors.forename: Susan
authors.initials: S
authors.lastname: McClory
authors.forename: Guido
authors.initials: G
authors.lastname: Marcucci
authors.forename: Rossana
authors.initials: R
authors.lastname: Trotta
authors.forename: Michael A
authors.initials: MA
authors.lastname: Caligiuri
mesh_terms: D019002:CD56 Antigen / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D019041:L-Selectin / Q000276:immunology; D016131:Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D051920:NK Cell Lectin-Like Receptor Subfamily D / Q000276:immunology*; D010766:Phosphorylation / Q000276:immunology; D050797:STAT4 Transcription Factor / Q000276:immunology
chemical_list: D019002:CD56 Antigen; C497869:KLRD1 protein, human; D051920:NK Cell Lectin-Like Receptor Subfamily D; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; D019041:L-Selectin; D018664:Interleukin-12; D007371:Interferon-gamma