TY - JOUR
T1 - CD94 surface density identifies a functional intermediary between the CD56bright and CD56dim human NK-cell subsets
AU - Yu, Jianhua
AU - Mao, Hsiaoyin C.
AU - Wei, Min
AU - Hughes, Tiffany
AU - Zhang, Jianying
AU - Park, Il Kyoo
AU - Liu, Shujun
AU - McClory, Susan
AU - Marcucci, Guido
AU - Trotta, Rossana
AU - Caligiuri, Michael A.
PY - 2010/1/14
Y1 - 2010/1/14
N2 - 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.
AB - 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.
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U2 - 10.1182/blood-2009-04-215491
DO - 10.1182/blood-2009-04-215491
M3 - Article
C2 - 19897577
AN - SCOPUS:75649122988
SN - 0006-4971
VL - 115
SP - 274
EP - 281
JO - Blood
JF - Blood
IS - 2
ER -