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), 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.
Perez
Sonia A
SA
Cancer Immunology Immunotherapy Center, Saint Savas Hospital, Athens, Greece. cacenter@otenet.gr
Sotiropoulou
Panagiota A
PA
Gkika
Dimitra G
DG
Mahaira
Louisa G
LG
Niarchos
Dimitrios K
DK
Gritzapis
Angelos D
AD
Kavalakis
Yiannis G
YG
Antsaklis
Aris I
AI
Baxevanis
Constantin N
CN
Papamichail
Michael
M
D000818:Animals; D002051:Burkitt Lymphoma / Q000473:pathology; D019002:CD56 Antigen / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured / Q000166:cytology / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D005312:Fetal Blood / Q000166:cytology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D016130:Immunophenotyping; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D019409:Interleukin-15 / Q000494:pharmacology; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000166:cytology*; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D008565:Membrane Proteins / Q000494:pharmacology; D051379:Mice; D009101:Multiple Myeloma / Q000473:pathology; D022423:Myeloid Cells / Q000145:classification*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D019002:CD56 Antigen; D019409:Interleukin-15; D018950:Lipopolysaccharide Receptors; D008565:Membrane Proteins; D014409:Tumor Necrosis Factor-alpha; C084881:flt3 ligand protein; D016753:Interleukin-10; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor