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Prepublished online as a Blood First Edition Paper on December 27, 2002; DOI 10.1182/blood-2002-05-1501.

Submitted May 22, 2002
Accepted December 17, 2002
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
Cancer Immunology Immunotherapy Center, Saint Savas Hospital, Athens, Greece
1st Obstetrics and Gynecology University Clinic, Alexandras Maternity Hospital, Athens, Greece
* Corresponding author; email: cacenter{at}otenet.gr.
NK cell differentiation from pluripotent CD34+ human hematopoietic stem cells (HSC) 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 setup with flt3-ligand (FL) and 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 LAK-sensitive tumor targets and producing high levels of IFN- , GM-CSF, TNF 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 less amounts of 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 zero levels by day 20. Approximately 60% of the CD56+ derived from the UCB/ACF or the UCB/CD14+ cells co-expressed CD14 by day 5. Taken altogether, our data support the role of CD14+ myeloid-like cells within UCB as a novel progenitor for lymphoid NK cells.

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