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Blood First Edition Paper, prepublished online November 6, 2009; DOI 10.1182/blood-2009-04-215491. This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Yu, J. Articles by Caligiuri, M. A. PubMed PubMed Citation Articles by Yu, J. Articles by Caligiuri, M. A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 8, 2009; accepted October 9, 2009. CD94 surface density identifies a functional intermediary between the CD56bright and CD56dim human NK cell subsets Jianhua Yu1, Hsiaoyin Charlene Mao1, Min Wei1, Tiffany Hughes1, Jianying Zhang2, Il-kyoo Park1, Shujun Liu3, Susan McClory1, Guido Marcucci4, Rossana Trotta1 and Michael A. Caligiuri1,3 1 Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, OH; 2 Center for Biostatistics, The Ohio State University, Columbus, OH; 3 Division of Hematology/Oncology, Department of Internal Medicine, The Ohio State University, Columbus, OH; 4 The Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute, Columbus, OH * Corresponding author; email: michael.caligiuri{at}osumc.edu Abstract Human CD56bright natural killer (NK) cells possess little or no killer immunoglobulin-like receptors (KIR), high IFN- production, but little cytotoxicity. CD56dim NK cells have high KIR expression, produce little IFN-, yet display high cytotoxicity. We hypothesized that if human NK maturation progresses from a CD56bright to a CD56dim phenotype, an intermediary NK cell must exist which demonstrates more functional overlap than these two subsets, and we utilized CD94 expression to test our hypothesis. CD94highCD56dim NK cells express CD62L, CD2, and KIR at levels between CD56bright and CD94lowCD56dim NK cells. CD94highCD56dim NK cells produce less monokine-induced IFN- than CD56bright NK cells but much more than CD94lowCD56dim NK cells due to differential IL-12-mediated STAT4 phosphorylation. CD94highCD56dim NK cells possess a higher level of granzyme B and perforin expression and CD94-mediated redirected killing than CD56bright NK cells but lower than CD94lowCD56dim NK cells. Collectively, our data suggest that density of CD94 surface expression on CD56dim NK cells identifies a functional and likely developmental intermediary between CD56bright and CD94lowCD56dim NK cells. This supports the notion that in vivo, human CD56bright NK cells progress through a continuum of differentiation that ends with a CD94lowCD56dim phenotype. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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