Adaptive NK cells can persist in patients with GATA2 mutation depleted of stem and progenitor cells.
Identifieur interne : 000358 ( PubMed/Corpus ); précédent : 000357; suivant : 000359Adaptive NK cells can persist in patients with GATA2 mutation depleted of stem and progenitor cells.
Auteurs : Heinrich Schlums ; Moonjung Jung ; Hongya Han ; Jakob Theorell ; Venetia Bigley ; Samuel C C. Chiang ; David S J. Allan ; Jan K. Davidson-Moncada ; Rachel E. Dickinson ; Tim D. Holmes ; Amy P. Hsu ; Danielle Townsley ; Thomas Winkler ; Weixin Wang ; P L Aukrust ; Ingvild Nord Y ; Katherine R. Calvo ; Steve M. Holland ; Matthew Collin ; Cynthia E. Dunbar ; Yenan T. BrycesonSource :
- Blood [ 1528-0020 ] ; 2017.
English descriptors
- KwdEn :
- Adolescent, Adult, Calmodulin-Binding Proteins (genetics), Calmodulin-Binding Proteins (immunology), Cell Proliferation, Child, Female, GATA2 Transcription Factor (genetics), GATA2 Transcription Factor (immunology), Hematopoietic Stem Cells (immunology), Humans, Interleukin-12 (genetics), Interleukin-12 (immunology), Interleukin-18 (genetics), Interleukin-18 (immunology), Killer Cells, Natural (immunology), Male, Middle Aged, Mutation, RNA-Binding Proteins (genetics), RNA-Binding Proteins (immunology), Receptors, IgE (genetics), Receptors, IgE (immunology), Syk Kinase (genetics), Syk Kinase (immunology), Transcription Factors (genetics), Transcription Factors (immunology).
- MESH :
- chemical , genetics : Calmodulin-Binding Proteins, GATA2 Transcription Factor, Interleukin-12, Interleukin-18, RNA-Binding Proteins, Receptors, IgE, Syk Kinase, Transcription Factors.
- chemical , immunology : Calmodulin-Binding Proteins, GATA2 Transcription Factor, Interleukin-12, Interleukin-18, RNA-Binding Proteins, Receptors, IgE, Syk Kinase, Transcription Factors.
- immunology : Hematopoietic Stem Cells, Killer Cells, Natural.
- Adolescent, Adult, Cell Proliferation, Child, Female, Humans, Male, Middle Aged, Mutation.
Abstract
Heterozygous GATA2 mutation is associated with immunodeficiency, lymphedema, and myelodysplastic syndrome. Disease presentation is variable, often coinciding with loss of circulating dendritic cells, monocytes, B cells, and natural killer (NK) cells. Nonetheless, in a proportion of patients carrying GATA2 mutation, NK cells persist. We found that peripheral blood NK cells in symptomatic patients uniformly lacked expression of the transcription factor promyelocytic leukemia zinc finger (PLZF), as well as expression of intracellular signaling proteins FcεRγ, spleen tyrosine kinase (SYK), and EWS/FLI1-Activated Transcript 2 (EAT-2) in a variegated manner. Moreover, consistent with an adaptive identity, NK cells from patients with GATA2 mutation displayed altered expression of cytotoxic granule constituents and produced interferon-γ upon Fc-receptor engagement but not following combined interleukin-12 (IL-12) and IL-18 stimulation. Canonical, PLZF-expressing NK cells were retained in asymptomatic carriers of GATA2 mutation. Developmentally, GATA-binding protein-2 (GATA-2) was expressed in hematopoietic stem cells, but not in NK-cell progenitors, CD3(-)CD56(bright), canonical, or adaptive CD3(-)CD56(dim) NK cells. Peripheral blood NK cells from individuals with GATA2 mutation proliferated normally in vitro, whereas lineage-negative progenitors displayed impaired NK-cell differentiation. In summary, adaptive NK cells can persist in patients with GATA2 mutation, even after NK-cell progenitors expire. Moreover, our data suggest that adaptive NK cells are more long-lived than canonical, immunoregulatory NK cells.
DOI: 10.1182/blood-2016-08-734236
PubMed: 28209719
Links to Exploration step
pubmed:28209719Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Adaptive NK cells can persist in patients with GATA2 mutation depleted of stem and progenitor cells.</title><author><name sortKey="Schlums, Heinrich" sort="Schlums, Heinrich" uniqKey="Schlums H" first="Heinrich" last="Schlums">Heinrich Schlums</name><affiliation><nlm:affiliation>Center for Hematology and Regenerative Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.</nlm:affiliation></affiliation></author><author><name sortKey="Jung, Moonjung" sort="Jung, Moonjung" uniqKey="Jung M" first="Moonjung" last="Jung">Moonjung Jung</name><affiliation><nlm:affiliation>Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.</nlm:affiliation></affiliation></author><author><name sortKey="Han, Hongya" sort="Han, Hongya" uniqKey="Han H" first="Hongya" last="Han">Hongya Han</name><affiliation><nlm:affiliation>Center for Hematology and Regenerative Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.</nlm:affiliation></affiliation></author><author><name sortKey="Theorell, Jakob" sort="Theorell, Jakob" uniqKey="Theorell J" first="Jakob" last="Theorell">Jakob Theorell</name><affiliation><nlm:affiliation>Center for Hematology and Regenerative Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.</nlm:affiliation></affiliation></author><author><name sortKey="Bigley, Venetia" sort="Bigley, Venetia" uniqKey="Bigley V" first="Venetia" last="Bigley">Venetia Bigley</name><affiliation><nlm:affiliation>Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Chiang, Samuel C C" sort="Chiang, Samuel C C" uniqKey="Chiang S" first="Samuel C C" last="Chiang">Samuel C C. Chiang</name><affiliation><nlm:affiliation>Center for Hematology and Regenerative Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.</nlm:affiliation></affiliation></author><author><name sortKey="Allan, David S J" sort="Allan, David S J" uniqKey="Allan D" first="David S J" last="Allan">David S J. Allan</name><affiliation><nlm:affiliation>Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.</nlm:affiliation></affiliation></author><author><name sortKey="Davidson Moncada, Jan K" sort="Davidson Moncada, Jan K" uniqKey="Davidson Moncada J" first="Jan K" last="Davidson-Moncada">Jan K. Davidson-Moncada</name><affiliation><nlm:affiliation>Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.</nlm:affiliation></affiliation></author><author><name sortKey="Dickinson, Rachel E" sort="Dickinson, Rachel E" uniqKey="Dickinson R" first="Rachel E" last="Dickinson">Rachel E. Dickinson</name><affiliation><nlm:affiliation>Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Holmes, Tim D" sort="Holmes, Tim D" uniqKey="Holmes T" first="Tim D" last="Holmes">Tim D. Holmes</name><affiliation><nlm:affiliation>Center for Hematology and Regenerative Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.</nlm:affiliation></affiliation></author><author><name sortKey="Hsu, Amy P" sort="Hsu, Amy P" uniqKey="Hsu A" first="Amy P" last="Hsu">Amy P. Hsu</name><affiliation><nlm:affiliation>Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.</nlm:affiliation></affiliation></author><author><name sortKey="Townsley, Danielle" sort="Townsley, Danielle" uniqKey="Townsley D" first="Danielle" last="Townsley">Danielle Townsley</name><affiliation><nlm:affiliation>Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.</nlm:affiliation></affiliation></author><author><name sortKey="Winkler, Thomas" sort="Winkler, Thomas" uniqKey="Winkler T" first="Thomas" last="Winkler">Thomas Winkler</name><affiliation><nlm:affiliation>Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.</nlm:affiliation></affiliation></author><author><name sortKey="Wang, Weixin" sort="Wang, Weixin" uniqKey="Wang W" first="Weixin" last="Wang">Weixin Wang</name><affiliation><nlm:affiliation>Department of Laboratory Medicine, National Institutes of Health Clinical Center, Bethesda, MD; and.</nlm:affiliation></affiliation></author><author><name sortKey="Aukrust, P L" sort="Aukrust, P L" uniqKey="Aukrust P" first="P L" last="Aukrust">P L Aukrust</name><affiliation><nlm:affiliation>Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, University of Oslo, Oslo, Norway.</nlm:affiliation></affiliation></author><author><name sortKey="Nord Y, Ingvild" sort="Nord Y, Ingvild" uniqKey="Nord Y I" first="Ingvild" last="Nord Y">Ingvild Nord Y</name><affiliation><nlm:affiliation>Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, University of Oslo, Oslo, Norway.</nlm:affiliation></affiliation></author><author><name sortKey="Calvo, Katherine R" sort="Calvo, Katherine R" uniqKey="Calvo K" first="Katherine R" last="Calvo">Katherine R. Calvo</name><affiliation><nlm:affiliation>Department of Laboratory Medicine, National Institutes of Health Clinical Center, Bethesda, MD; and.</nlm:affiliation></affiliation></author><author><name sortKey="Holland, Steve M" sort="Holland, Steve M" uniqKey="Holland S" first="Steve M" last="Holland">Steve M. Holland</name><affiliation><nlm:affiliation>Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.</nlm:affiliation></affiliation></author><author><name sortKey="Collin, Matthew" sort="Collin, Matthew" uniqKey="Collin M" first="Matthew" last="Collin">Matthew Collin</name><affiliation><nlm:affiliation>Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Dunbar, Cynthia E" sort="Dunbar, Cynthia E" uniqKey="Dunbar C" first="Cynthia E" last="Dunbar">Cynthia E. Dunbar</name><affiliation><nlm:affiliation>Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.</nlm:affiliation></affiliation></author><author><name sortKey="Bryceson, Yenan T" sort="Bryceson, Yenan T" uniqKey="Bryceson Y" first="Yenan T" last="Bryceson">Yenan T. Bryceson</name><affiliation><nlm:affiliation>Center for Hematology and Regenerative Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2017">2017</date><idno type="RBID">pubmed:28209719</idno><idno type="pmid">28209719</idno><idno type="doi">10.1182/blood-2016-08-734236</idno><idno type="wicri:Area/PubMed/Corpus">000358</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000358</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Adaptive NK cells can persist in patients with GATA2 mutation depleted of stem and progenitor cells.</title><author><name sortKey="Schlums, Heinrich" sort="Schlums, Heinrich" uniqKey="Schlums H" first="Heinrich" last="Schlums">Heinrich Schlums</name><affiliation><nlm:affiliation>Center for Hematology and Regenerative Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.</nlm:affiliation></affiliation></author><author><name sortKey="Jung, Moonjung" sort="Jung, Moonjung" uniqKey="Jung M" first="Moonjung" last="Jung">Moonjung Jung</name><affiliation><nlm:affiliation>Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.</nlm:affiliation></affiliation></author><author><name sortKey="Han, Hongya" sort="Han, Hongya" uniqKey="Han H" first="Hongya" last="Han">Hongya Han</name><affiliation><nlm:affiliation>Center for Hematology and Regenerative Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.</nlm:affiliation></affiliation></author><author><name sortKey="Theorell, Jakob" sort="Theorell, Jakob" uniqKey="Theorell J" first="Jakob" last="Theorell">Jakob Theorell</name><affiliation><nlm:affiliation>Center for Hematology and Regenerative Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.</nlm:affiliation></affiliation></author><author><name sortKey="Bigley, Venetia" sort="Bigley, Venetia" uniqKey="Bigley V" first="Venetia" last="Bigley">Venetia Bigley</name><affiliation><nlm:affiliation>Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Chiang, Samuel C C" sort="Chiang, Samuel C C" uniqKey="Chiang S" first="Samuel C C" last="Chiang">Samuel C C. Chiang</name><affiliation><nlm:affiliation>Center for Hematology and Regenerative Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.</nlm:affiliation></affiliation></author><author><name sortKey="Allan, David S J" sort="Allan, David S J" uniqKey="Allan D" first="David S J" last="Allan">David S J. Allan</name><affiliation><nlm:affiliation>Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.</nlm:affiliation></affiliation></author><author><name sortKey="Davidson Moncada, Jan K" sort="Davidson Moncada, Jan K" uniqKey="Davidson Moncada J" first="Jan K" last="Davidson-Moncada">Jan K. Davidson-Moncada</name><affiliation><nlm:affiliation>Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.</nlm:affiliation></affiliation></author><author><name sortKey="Dickinson, Rachel E" sort="Dickinson, Rachel E" uniqKey="Dickinson R" first="Rachel E" last="Dickinson">Rachel E. Dickinson</name><affiliation><nlm:affiliation>Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Holmes, Tim D" sort="Holmes, Tim D" uniqKey="Holmes T" first="Tim D" last="Holmes">Tim D. Holmes</name><affiliation><nlm:affiliation>Center for Hematology and Regenerative Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.</nlm:affiliation></affiliation></author><author><name sortKey="Hsu, Amy P" sort="Hsu, Amy P" uniqKey="Hsu A" first="Amy P" last="Hsu">Amy P. Hsu</name><affiliation><nlm:affiliation>Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.</nlm:affiliation></affiliation></author><author><name sortKey="Townsley, Danielle" sort="Townsley, Danielle" uniqKey="Townsley D" first="Danielle" last="Townsley">Danielle Townsley</name><affiliation><nlm:affiliation>Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.</nlm:affiliation></affiliation></author><author><name sortKey="Winkler, Thomas" sort="Winkler, Thomas" uniqKey="Winkler T" first="Thomas" last="Winkler">Thomas Winkler</name><affiliation><nlm:affiliation>Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.</nlm:affiliation></affiliation></author><author><name sortKey="Wang, Weixin" sort="Wang, Weixin" uniqKey="Wang W" first="Weixin" last="Wang">Weixin Wang</name><affiliation><nlm:affiliation>Department of Laboratory Medicine, National Institutes of Health Clinical Center, Bethesda, MD; and.</nlm:affiliation></affiliation></author><author><name sortKey="Aukrust, P L" sort="Aukrust, P L" uniqKey="Aukrust P" first="P L" last="Aukrust">P L Aukrust</name><affiliation><nlm:affiliation>Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, University of Oslo, Oslo, Norway.</nlm:affiliation></affiliation></author><author><name sortKey="Nord Y, Ingvild" sort="Nord Y, Ingvild" uniqKey="Nord Y I" first="Ingvild" last="Nord Y">Ingvild Nord Y</name><affiliation><nlm:affiliation>Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, University of Oslo, Oslo, Norway.</nlm:affiliation></affiliation></author><author><name sortKey="Calvo, Katherine R" sort="Calvo, Katherine R" uniqKey="Calvo K" first="Katherine R" last="Calvo">Katherine R. Calvo</name><affiliation><nlm:affiliation>Department of Laboratory Medicine, National Institutes of Health Clinical Center, Bethesda, MD; and.</nlm:affiliation></affiliation></author><author><name sortKey="Holland, Steve M" sort="Holland, Steve M" uniqKey="Holland S" first="Steve M" last="Holland">Steve M. Holland</name><affiliation><nlm:affiliation>Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.</nlm:affiliation></affiliation></author><author><name sortKey="Collin, Matthew" sort="Collin, Matthew" uniqKey="Collin M" first="Matthew" last="Collin">Matthew Collin</name><affiliation><nlm:affiliation>Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Dunbar, Cynthia E" sort="Dunbar, Cynthia E" uniqKey="Dunbar C" first="Cynthia E" last="Dunbar">Cynthia E. Dunbar</name><affiliation><nlm:affiliation>Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.</nlm:affiliation></affiliation></author><author><name sortKey="Bryceson, Yenan T" sort="Bryceson, Yenan T" uniqKey="Bryceson Y" first="Yenan T" last="Bryceson">Yenan T. Bryceson</name><affiliation><nlm:affiliation>Center for Hematology and Regenerative Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Blood</title><idno type="eISSN">1528-0020</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adolescent</term><term>Adult</term><term>Calmodulin-Binding Proteins (genetics)</term><term>Calmodulin-Binding Proteins (immunology)</term><term>Cell Proliferation</term><term>Child</term><term>Female</term><term>GATA2 Transcription Factor (genetics)</term><term>GATA2 Transcription Factor (immunology)</term><term>Hematopoietic Stem Cells (immunology)</term><term>Humans</term><term>Interleukin-12 (genetics)</term><term>Interleukin-12 (immunology)</term><term>Interleukin-18 (genetics)</term><term>Interleukin-18 (immunology)</term><term>Killer Cells, Natural (immunology)</term><term>Male</term><term>Middle Aged</term><term>Mutation</term><term>RNA-Binding Proteins (genetics)</term><term>RNA-Binding Proteins (immunology)</term><term>Receptors, IgE (genetics)</term><term>Receptors, IgE (immunology)</term><term>Syk Kinase (genetics)</term><term>Syk Kinase (immunology)</term><term>Transcription Factors (genetics)</term><term>Transcription Factors (immunology)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Calmodulin-Binding Proteins</term><term>GATA2 Transcription Factor</term><term>Interleukin-12</term><term>Interleukin-18</term><term>RNA-Binding Proteins</term><term>Receptors, IgE</term><term>Syk Kinase</term><term>Transcription Factors</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Calmodulin-Binding Proteins</term><term>GATA2 Transcription Factor</term><term>Interleukin-12</term><term>Interleukin-18</term><term>RNA-Binding Proteins</term><term>Receptors, IgE</term><term>Syk Kinase</term><term>Transcription Factors</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Hematopoietic Stem Cells</term><term>Killer Cells, Natural</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adolescent</term><term>Adult</term><term>Cell Proliferation</term><term>Child</term><term>Female</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Mutation</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Heterozygous GATA2 mutation is associated with immunodeficiency, lymphedema, and myelodysplastic syndrome. Disease presentation is variable, often coinciding with loss of circulating dendritic cells, monocytes, B cells, and natural killer (NK) cells. Nonetheless, in a proportion of patients carrying GATA2 mutation, NK cells persist. We found that peripheral blood NK cells in symptomatic patients uniformly lacked expression of the transcription factor promyelocytic leukemia zinc finger (PLZF), as well as expression of intracellular signaling proteins FcεRγ, spleen tyrosine kinase (SYK), and EWS/FLI1-Activated Transcript 2 (EAT-2) in a variegated manner. Moreover, consistent with an adaptive identity, NK cells from patients with GATA2 mutation displayed altered expression of cytotoxic granule constituents and produced interferon-γ upon Fc-receptor engagement but not following combined interleukin-12 (IL-12) and IL-18 stimulation. Canonical, PLZF-expressing NK cells were retained in asymptomatic carriers of GATA2 mutation. Developmentally, GATA-binding protein-2 (GATA-2) was expressed in hematopoietic stem cells, but not in NK-cell progenitors, CD3(-)CD56(bright), canonical, or adaptive CD3(-)CD56(dim) NK cells. Peripheral blood NK cells from individuals with GATA2 mutation proliferated normally in vitro, whereas lineage-negative progenitors displayed impaired NK-cell differentiation. In summary, adaptive NK cells can persist in patients with GATA2 mutation, even after NK-cell progenitors expire. Moreover, our data suggest that adaptive NK cells are more long-lived than canonical, immunoregulatory NK cells.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">28209719</PMID><DateCreated><Year>2017</Year><Month>02</Month><Day>17</Day></DateCreated><DateCompleted><Year>2017</Year><Month>08</Month><Day>10</Day></DateCompleted><DateRevised><Year>2017</Year><Month>08</Month><Day>10</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1528-0020</ISSN><JournalIssue CitedMedium="Internet"><Volume>129</Volume><Issue>14</Issue><PubDate><Year>2017</Year><Month>Apr</Month><Day>06</Day></PubDate></JournalIssue><Title>Blood</Title><ISOAbbreviation>Blood</ISOAbbreviation></Journal><ArticleTitle>Adaptive NK cells can persist in patients with GATA2 mutation depleted of stem and progenitor cells.</ArticleTitle><Pagination><MedlinePgn>1927-1939</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1182/blood-2016-08-734236</ELocationID><Abstract><AbstractText>Heterozygous GATA2 mutation is associated with immunodeficiency, lymphedema, and myelodysplastic syndrome. Disease presentation is variable, often coinciding with loss of circulating dendritic cells, monocytes, B cells, and natural killer (NK) cells. Nonetheless, in a proportion of patients carrying GATA2 mutation, NK cells persist. We found that peripheral blood NK cells in symptomatic patients uniformly lacked expression of the transcription factor promyelocytic leukemia zinc finger (PLZF), as well as expression of intracellular signaling proteins FcεRγ, spleen tyrosine kinase (SYK), and EWS/FLI1-Activated Transcript 2 (EAT-2) in a variegated manner. Moreover, consistent with an adaptive identity, NK cells from patients with GATA2 mutation displayed altered expression of cytotoxic granule constituents and produced interferon-γ upon Fc-receptor engagement but not following combined interleukin-12 (IL-12) and IL-18 stimulation. Canonical, PLZF-expressing NK cells were retained in asymptomatic carriers of GATA2 mutation. Developmentally, GATA-binding protein-2 (GATA-2) was expressed in hematopoietic stem cells, but not in NK-cell progenitors, CD3(-)CD56(bright), canonical, or adaptive CD3(-)CD56(dim) NK cells. Peripheral blood NK cells from individuals with GATA2 mutation proliferated normally in vitro, whereas lineage-negative progenitors displayed impaired NK-cell differentiation. In summary, adaptive NK cells can persist in patients with GATA2 mutation, even after NK-cell progenitors expire. Moreover, our data suggest that adaptive NK cells are more long-lived than canonical, immunoregulatory NK cells.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Schlums</LastName><ForeName>Heinrich</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Center for Hematology and Regenerative Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jung</LastName><ForeName>Moonjung</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Han</LastName><ForeName>Hongya</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Center for Hematology and Regenerative Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Theorell</LastName><ForeName>Jakob</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Center for Hematology and Regenerative Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bigley</LastName><ForeName>Venetia</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chiang</LastName><ForeName>Samuel C C</ForeName><Initials>SC</Initials><AffiliationInfo><Affiliation>Center for Hematology and Regenerative Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Allan</LastName><ForeName>David S J</ForeName><Initials>DS</Initials><AffiliationInfo><Affiliation>Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Davidson-Moncada</LastName><ForeName>Jan K</ForeName><Initials>JK</Initials><AffiliationInfo><Affiliation>Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dickinson</LastName><ForeName>Rachel E</ForeName><Initials>RE</Initials><AffiliationInfo><Affiliation>Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Holmes</LastName><ForeName>Tim D</ForeName><Initials>TD</Initials><AffiliationInfo><Affiliation>Center for Hematology and Regenerative Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Broegelmann Research Laboratory, Department of Clinical Sciences, University of Bergen, Bergen, Norway.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hsu</LastName><ForeName>Amy P</ForeName><Initials>AP</Initials><AffiliationInfo><Affiliation>Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Townsley</LastName><ForeName>Danielle</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Winkler</LastName><ForeName>Thomas</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Weixin</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>Department of Laboratory Medicine, National Institutes of Health Clinical Center, Bethesda, MD; and.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Aukrust</LastName><ForeName>Pål</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, University of Oslo, Oslo, Norway.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nordøy</LastName><ForeName>Ingvild</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, University of Oslo, Oslo, Norway.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Calvo</LastName><ForeName>Katherine R</ForeName><Initials>KR</Initials><AffiliationInfo><Affiliation>Department of Laboratory Medicine, National Institutes of Health Clinical Center, Bethesda, MD; and.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Holland</LastName><ForeName>Steve M</ForeName><Initials>SM</Initials><AffiliationInfo><Affiliation>Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Collin</LastName><ForeName>Matthew</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dunbar</LastName><ForeName>Cynthia E</ForeName><Initials>CE</Initials><AffiliationInfo><Affiliation>Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bryceson</LastName><ForeName>Yenan T</ForeName><Initials>YT</Initials><AffiliationInfo><Affiliation>Center for Hematology and Regenerative Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Broegelmann Research Laboratory, Department of Clinical Sciences, University of Bergen, Bergen, Norway.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2017</Year><Month>02</Month><Day>16</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Blood</MedlineTA><NlmUniqueID>7603509</NlmUniqueID><ISSNLinking>0006-4971</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D002148">Calmodulin-Binding Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C500986">EWSR1 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C543372">FcepsilonRI gamma-chain, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D050989">GATA2 Transcription 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MajorTopicYN="N">Interleukin-18</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007694" MajorTopicYN="N">Killer Cells, Natural</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009154" MajorTopicYN="Y">Mutation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016601" MajorTopicYN="N">RNA-Binding Proteins</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D017455" MajorTopicYN="N">Receptors, IgE</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000072377" MajorTopicYN="N">Syk Kinase</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014157" MajorTopicYN="N">Transcription Factors</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2016</Year><Month>08</Month><Day>17</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2017</Year><Month>02</Month><Day>02</Day></PubMedPubDate><PubMedPubDate 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