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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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2002-05-1501v1
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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-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.

© 2003 by The American Society of Hematology.
 

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