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

• Published in: Blood Vol. 101; no. 9; pp. 3444 - 3450
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01.05.2003; The Americain Society of Hematology; American Society of Hematology
• 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; Natural killer cell; Human; Phenotype; Cell line; Stem cell; Umbilical cord; Cell differentiation; Myeloid cell; Myeloid-like NK cell; Blood; Progenitor cell
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2002-05-1501

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.