TY - JOUR
TI - A novel myeloid-like NK cell progenitor in human umbilical cord blood
AU - Perez, SA
AU - Sotiropoulou, PA
AU - Gkika, DG
AU - Mahaira, LG and
AU - Niarchos, DK
AU - Gritzapis, AD
AU - Kavalakis, YG
AU - Antsaklis, AI and
AU - Baxevanis, CN
AU - Papamichail, M
JO - Blood advances
PY - 2003
VL - 101
TODO - 9
SP - 3444-3450
PB - AMER SOC HEMATOLOGY
SN - null
TODO - 10.1182/blood-2002-05-1501
TODO - null
TODO - Natural killer (NK) cell differentiation from pluripotent CD34(+) human
hematopoietic stem cells or oligopotent lymphoid progenitors has already
been reported. In the present study, long-term cultures of the
CD56(-)/CD34(-) myeloid-like adherent cell fraction (ACF) from umbilical
cord blood (UCB), characterized by the expression of CD14(+) as well as
other myeloid markers, were set up with flt3 ligand (FL) and
interleukin-15 (IL-15). The UCB/ACF gradually expressed the CD56 marker,
which reached fairly high levels (approximately 90% of the cells were
CD56(+)) by day 15. FL plus IL-15-driven ACF/CD56(+) cells progressively
expressed a mature NK functional program lysing both NK- and
lymphokine-activate killer (LAK)sensitive tumor targets and producing
high levels of interferon-gamma (IFN-gamma), granulocyte-macrophage
colony-stimulating factor, tumor necrosis factor alpha, and IL-10 upon
stimulation with IL-12 and IL-18. Similar results were obtained when
highly purified CD14(+) cells from UCB were cultured with FL and IL-15.
In contrast, UCB/CD34(+) cells cultured under the same conditions showed
a delayed expression of CD56 and behaved functionally differently in
that they exhibited NK but not LAK cytotoxicity and produced
significantly fewer cytokines. Kinetic studies on the phenotype of
UCB/ACF or UCB/CD14(+) cells cultured in the presence of FL and IL-15
showed a rapid decrease in CD14 expression after day 5, which reached
levels of zero by day 20. Approximately 60% of the CD56(+) derived from
the UCB/ACF or the UCB/CD14(+) cells coexpressed CD14 by day 5. Taken
together, our data support the role of CD14(+) myeloid-like cells within
UCB as a novel progenitor for lymphoid NK cells. (C) 2003 by The
American Society of Hematology.
ER -