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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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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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.</description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood-2002-05-1501</identifier><identifier>PMID: 12506032</identifier><language>eng</language><publisher>Washington, DC: Elsevier Inc</publisher><subject>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</subject><ispartof>Blood, 2003-05, Vol.101 (9), p.3444-3450</ispartof><rights>2003 American Society of Hematology</rights><rights>2003 INIST-CNRS</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c509t-6c22e7623aa3baa36ca25bf3a27950f809e5c0a693d112b8da9bf4159eb5afbe3</citedby><cites>FETCH-LOGICAL-c509t-6c22e7623aa3baa36ca25bf3a27950f809e5c0a693d112b8da9bf4159eb5afbe3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,777,781,882,27905,27906</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14758898$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12506032$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.univ-lille.fr/hal-04040069$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Perez, Sonia A.</creatorcontrib><creatorcontrib>Sotiropoulou, Panagiota A.</creatorcontrib><creatorcontrib>Gkika, Dimitra G.</creatorcontrib><creatorcontrib>Mahaira, Louisa G.</creatorcontrib><creatorcontrib>Niarchos, Dimitrios K.</creatorcontrib><creatorcontrib>Gritzapis, Angelos D.</creatorcontrib><creatorcontrib>Kavalakis, Yiannis G.</creatorcontrib><creatorcontrib>Antsaklis, Aris I.</creatorcontrib><creatorcontrib>Baxevanis, Constantin N.</creatorcontrib><creatorcontrib>Papamichail, Michael</creatorcontrib><title>A novel myeloid-like NK cell progenitor in human umbilical cord blood</title><title>Blood</title><addtitle>Blood</addtitle><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.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Burkitt Lymphoma - pathology</subject><subject>CD56 Antigen - biosynthesis</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell differentiation, maturation, development, hematopoiesis</subject><subject>Cell physiology</subject><subject>Cells, Cultured - cytology</subject><subject>Cells, Cultured - metabolism</subject><subject>Cytotoxicity, Immunologic</subject><subject>Fetal Blood - cytology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Granulocyte-Macrophage Colony-Stimulating Factor - biosynthesis</subject><subject>Hematopoietic Stem Cells - cytology</subject><subject>Hematopoietic Stem Cells - drug effects</subject><subject>Humans</subject><subject>Immunophenotyping</subject><subject>Infant, Newborn</subject><subject>Interferon-gamma - biosynthesis</subject><subject>Interleukin-10 - biosynthesis</subject><subject>Interleukin-15 - pharmacology</subject><subject>K562 Cells</subject><subject>Killer Cells, Natural - cytology</subject><subject>Life Sciences</subject><subject>Lipopolysaccharide Receptors - biosynthesis</subject><subject>Membrane Proteins - pharmacology</subject><subject>Mice</subject><subject>Molecular and cellular biology</subject><subject>Multiple Myeloma - pathology</subject><subject>Myeloid Cells - classification</subject><subject>Tumor Cells, Cultured</subject><subject>Tumor Necrosis Factor-alpha - biosynthesis</subject><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMGKFDEQhoMo7uzqC3iQXBQ8RCtJp7sDXoZl3RUHveg5JOlqN5rurMn0wL696Z3BvUkoAsVXRf0fIa84vOe8Fx9cTGlgAkAwUIwr4E_IhivRs9qCp2QDAC1rdMfPyHkpvwB4I4V6Ts64UNCCFBtytaVzOmCk0z3GFAYWw2-kX79QjzHSu5x-4hz2KdMw09tlsjNdJhdi8DZSn_JAH454QZ6NNhZ8efovyI9PV98vb9ju2_Xny-2OeQV6z1ovBHatkNZKV6v1Vig3Sis6rWDsQaPyYFstB86F6wer3dhwpdEpOzqUF-Tdce-tjeYuh8nme5NsMDfbnVl70NQHrT7wyr49sjXEnwXL3kyhrKnsjGkpppMCml52FRRH0OdUSsbx32YOZhVtHjKaVbQBZVbRdej1afviJhweR05mK_DmBNhSZY3Zzj6UR67pVN_rvnIfjxxWb4eA2RQfcPY4hIx-b4YU_nfHX2zume8</recordid><startdate>20030501</startdate><enddate>20030501</enddate><creator>Perez, Sonia A.</creator><creator>Sotiropoulou, Panagiota A.</creator><creator>Gkika, Dimitra G.</creator><creator>Mahaira, Louisa G.</creator><creator>Niarchos, Dimitrios K.</creator><creator>Gritzapis, Angelos D.</creator><creator>Kavalakis, Yiannis G.</creator><creator>Antsaklis, Aris I.</creator><creator>Baxevanis, Constantin N.</creator><creator>Papamichail, Michael</creator><general>Elsevier Inc</general><general>The Americain Society of Hematology</general><general>American Society of Hematology</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>1XC</scope></search><sort><creationdate>20030501</creationdate><title>A novel myeloid-like NK cell progenitor in human umbilical cord blood</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c509t-6c22e7623aa3baa36ca25bf3a27950f809e5c0a693d112b8da9bf4159eb5afbe3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Burkitt Lymphoma - pathology</topic><topic>CD56 Antigen - biosynthesis</topic><topic>Cell Differentiation - drug effects</topic><topic>Cell differentiation, maturation, development, hematopoiesis</topic><topic>Cell physiology</topic><topic>Cells, Cultured - cytology</topic><topic>Cells, Cultured - metabolism</topic><topic>Cytotoxicity, Immunologic</topic><topic>Fetal Blood - cytology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Granulocyte-Macrophage Colony-Stimulating Factor - biosynthesis</topic><topic>Hematopoietic Stem Cells - cytology</topic><topic>Hematopoietic Stem Cells - drug effects</topic><topic>Humans</topic><topic>Immunophenotyping</topic><topic>Infant, Newborn</topic><topic>Interferon-gamma - biosynthesis</topic><topic>Interleukin-10 - biosynthesis</topic><topic>Interleukin-15 - pharmacology</topic><topic>K562 Cells</topic><topic>Killer Cells, Natural - cytology</topic><topic>Life Sciences</topic><topic>Lipopolysaccharide Receptors - biosynthesis</topic><topic>Membrane Proteins - pharmacology</topic><topic>Mice</topic><topic>Molecular and cellular biology</topic><topic>Multiple Myeloma - pathology</topic><topic>Myeloid Cells - classification</topic><topic>Tumor Cells, Cultured</topic><topic>Tumor Necrosis Factor-alpha - biosynthesis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Perez, Sonia A.</creatorcontrib><creatorcontrib>Sotiropoulou, Panagiota A.</creatorcontrib><creatorcontrib>Gkika, Dimitra G.</creatorcontrib><creatorcontrib>Mahaira, Louisa G.</creatorcontrib><creatorcontrib>Niarchos, Dimitrios K.</creatorcontrib><creatorcontrib>Gritzapis, Angelos D.</creatorcontrib><creatorcontrib>Kavalakis, Yiannis G.</creatorcontrib><creatorcontrib>Antsaklis, Aris I.</creatorcontrib><creatorcontrib>Baxevanis, Constantin N.</creatorcontrib><creatorcontrib>Papamichail, Michael</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Blood</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Perez, Sonia A.</au><au>Sotiropoulou, Panagiota A.</au><au>Gkika, Dimitra G.</au><au>Mahaira, Louisa G.</au><au>Niarchos, Dimitrios K.</au><au>Gritzapis, Angelos D.</au><au>Kavalakis, Yiannis G.</au><au>Antsaklis, Aris I.</au><au>Baxevanis, Constantin N.</au><au>Papamichail, Michael</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A novel myeloid-like NK cell progenitor in human umbilical cord blood</atitle><jtitle>Blood</jtitle><addtitle>Blood</addtitle><date>2003-05-01</date><risdate>2003</risdate><volume>101</volume><issue>9</issue><spage>3444</spage><epage>3450</epage><pages>3444-3450</pages><issn>0006-4971</issn><eissn>1528-0020</eissn><abstract>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.</abstract><cop>Washington, DC</cop><pub>Elsevier Inc</pub><pmid>12506032</pmid><doi>10.1182/blood-2002-05-1501</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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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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