CD56bright human NK cells differentiate into CD56dim cells: role of contact with peripheral fibroblasts

A Chan, DL Hong, A Atzberger… - The Journal of …, 2007 - journals.aai.org
A Chan, DL Hong, A Atzberger, S Kollnberger, AD Filer, CD Buckley, A McMichael, T Enver…
The Journal of Immunology, 2007journals.aai.org
Human NK cells are divided into CD56 bright CD16− cells and CD56 dim CD16+ cells. We
tested the hypothesis that CD56 bright NK cells can differentiate into CD56 dim cells by
prospectively isolating and culturing each NK subset in vitro and in vivo. Our results show
that CD56 bright cells can differentiate into CD56 dim both in vitro, in the presence of
synovial fibroblasts, and in vivo, upon transfer into NOD-SCID mice. In vitro, this
differentiation was inhibited by fibroblast growth factor receptor-1 Ab, demonstrating a role of …
Abstract
Human NK cells are divided into CD56 bright CD16− cells and CD56 dim CD16+ cells. We tested the hypothesis that CD56 bright NK cells can differentiate into CD56 dim cells by prospectively isolating and culturing each NK subset in vitro and in vivo. Our results show that CD56 bright cells can differentiate into CD56 dim both in vitro, in the presence of synovial fibroblasts, and in vivo, upon transfer into NOD-SCID mice. In vitro, this differentiation was inhibited by fibroblast growth factor receptor-1 Ab, demonstrating a role of the CD56 and fibroblast growth factor receptor-1 interaction in this process. Differentiated CD56 dim cells had reduced IFN-γ production but increased perforin expression and cytolysis of cell line K562 targets. Flow cytometric fluorescent in situ hybridization demonstrated that CD56 bright NK cells had longer telomere length compared with CD56 dim NK cells, implying the former are less mature. Our data support a linear differentiation model of human NK development in which immature CD56 bright NK cells can differentiate into CD56 dim cells.
journals.aai.org