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Prepublished online as a Blood First Edition Paper on December 27, 2002; DOI 10.1182/blood-2002-05-1501.
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Blood, 1 May 2003, Vol. 101, No. 9, pp. 3444-3450
HEMATOPOIESIS
A novel myeloid-like NK cell progenitor in human umbilical cord
blood
Sonia A. Perez,
Panagiota A. Sotiropoulou,
Dimitra G. Gkika,
Louisa G. Mahaira,
Dimitrios K. Niarchos,
Angelos D. Gritzapis,
Yiannis G. Kavalakis,
Aris I. Antsaklis,
Constantin N. Baxevanis, and
Michael Papamichail
From the Cancer Immunology Immunotherapy
Center, Saint Savas Hospital, Athens; and the First Obstetrics and
Gynecology University Clinic, Alexandras Maternity Hospital, Athens,
Greece.
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- (IFN- ), granulocyte-macrophage colony-stimulating
factor, tumor necrosis factor , 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.

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