CD94 surface density identifies a functional intermediary between the CD56bright and CD56dim human NK-cell subsets

Jianhua Yu, Hsiaoyin C. Mao, Min Wei, Tiffany Hughes, Jianying Zhang, Il Kyoo Park, Shujun Liu, Susan McClory, Guido Marcucci, Rossana Trotta, Michael A. Caligiuri

Research output: Contribution to journalArticlepeer-review

191 Scopus citations


Human CD56bright natural killer (NK) cells possess little or no killer immunoglobulin-like receptors (KIRs), high interferon-γ (IFN-γ) production, but little cytotoxicity. CD56dim NK cells have high KIR expression, produce little IFN-γ, 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 2 subsets, and we used CD94 expression to test our hypothesis. CD94highCD56 dim NK cells express CD62L, CD2, and KIR at levels between CD56 bright and CD94lowCD56dim NK cells. CD94 high CD56dim NK cells produce less monokine-induced IFN-γ than CD56bright NK cells but much more than CD94 lowCD56dim NK cells because of differential interleukin-12-mediated STAT4 phosphorylation. CD94high CD56 dim 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 the density of CD94 surface expression on CD56dim NK cells identifies a functional and likely developmental intermediary between CD56bright and CD94lowCD56 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 CD94lowCD56dim phenotype.

Original languageEnglish (US)
Pages (from-to)274-281
Number of pages8
Issue number2
StatePublished - Jan 14 2010
Externally publishedYes


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