A novel myeloid-like NK cell progenitor in human umbilical cord blood

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), characte...

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Veröffentlicht in:Blood 2003-05, Vol.101 (9), p.3444-3450
Hauptverfasser: Perez, Sonia A., Sotiropoulou, Panagiota A., Gkika, Dimitra G., Mahaira, Louisa G., Niarchos, Dimitrios K., Gritzapis, Angelos D., Kavalakis, Yiannis G., Antsaklis, Aris I., Baxevanis, Constantin N., Papamichail, Michael
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container_end_page 3450
container_issue 9
container_start_page 3444
container_title Blood
container_volume 101
creator Perez, Sonia A.
Sotiropoulou, Panagiota A.
Gkika, Dimitra G.
Mahaira, Louisa G.
Niarchos, Dimitrios K.
Gritzapis, Angelos D.
Kavalakis, Yiannis G.
Antsaklis, Aris I.
Baxevanis, Constantin N.
Papamichail, Michael
description 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-γ (IFN-γ), granulocyte-macrophage colony-stimulating factor, tumor necrosis factor α, 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.
doi_str_mv 10.1182/blood-2002-05-1501
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subjects Animals
Biological and medical sciences
Burkitt Lymphoma - pathology
CD56 Antigen - biosynthesis
Cell Differentiation - drug effects
Cell differentiation, maturation, development, hematopoiesis
Cell physiology
Cells, Cultured - cytology
Cells, Cultured - metabolism
Cytotoxicity, Immunologic
Fetal Blood - cytology
Fundamental and applied biological sciences. Psychology
Granulocyte-Macrophage Colony-Stimulating Factor - biosynthesis
Hematopoietic Stem Cells - cytology
Hematopoietic Stem Cells - drug effects
Humans
Immunophenotyping
Infant, Newborn
Interferon-gamma - biosynthesis
Interleukin-10 - biosynthesis
Interleukin-15 - pharmacology
K562 Cells
Killer Cells, Natural - cytology
Life Sciences
Lipopolysaccharide Receptors - biosynthesis
Membrane Proteins - pharmacology
Mice
Molecular and cellular biology
Multiple Myeloma - pathology
Myeloid Cells - classification
Tumor Cells, Cultured
Tumor Necrosis Factor-alpha - biosynthesis
title A novel myeloid-like NK cell progenitor in human umbilical cord blood
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