Natural Killer Cells from Patients with Recombinase-Activating Gene and Non-Homologous End Joining Gene Defects Comprise a Higher Frequency of CD56bright NKG2A+++ Cells, and Yet Display Increased Degranulation and Higher Perforin Content

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dc.contributor.authorDobbs, Kerry
dc.contributor.authorTabellini, Giovanna
dc.contributor.authorCalzoni, Enrica
dc.contributor.authorPatrizi, Ornella
dc.contributor.authorMartinez, Paula
dc.contributor.authorGiliani, Silvia Clara
dc.contributor.authorMoratto, Daniele
dc.date.accessioned2024-02-23T14:34:56Z
dc.date.available2024-02-23T14:34:56Z
dc.date.issued2017
dc.departmentNEÜen_US
dc.description.abstractMutations of the recombinase-activating genes 1 and 2 (RAG1 and RAG2) in humans are associated with a broad range of phenotypes. For patients with severe clinical presentation, hematopoietic stem cell transplantation (HSCT) represents the only curative treatment; however, high rates of graft failure and incomplete immune reconstitution have been observed, especially after unconditioned haploidentical transplantation. Studies in mice have shown that Rag-/-natural killer (NK) cells have a mature phenotype, reduced fitness, and increased cytotoxicity. We aimed to analyze NK cell phenotype and function in patients with mutations in RAG and in non-homologous end joining (NHEJ) genes. Here, we provide evidence that NK cells from these patients have an immature phenotype, with significant expansion of CD56(bright) CD16(-/int) CD57(-cells), yet increased degranulation and high perforin content. Correlation was observed between in vitro recombinase activity of the mutant proteins, NK cell abnormalities, and in vivo clinical phenotype. Addition of serotherapy in the conditioning regimen, with the aim of depleting the autologous NK cell compartment, may be important to facilitate engraftment and immune reconstitution in patients with RAG and NHEJ defects treated by HSCT.en_US
dc.description.sponsorshipDivision of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health; National Institute of Allergy and Infectious Diseases, National Institutes of Health [2R01AI100887]en_US
dc.description.sponsorshipFunding for this study was provided in part by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. This work was also supported by grant 2R01AI100887 from the National Institute of Allergy and Infectious Diseases, National Institutes of Health (to JM). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does the mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.en_US
dc.identifier.doi10.3389/fimmu.2017.00798
dc.identifier.issn1664-3224
dc.identifier.pmid28769923en_US
dc.identifier.scopus2-s2.0-85025431730en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.3389/fimmu.2017.00798
dc.identifier.urihttps://hdl.handle.net/20.500.12452/15823
dc.identifier.volume8en_US
dc.identifier.wosWOS:000405547800001en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherFrontiers Media Saen_US
dc.relation.ispartofFrontiers In Immunologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectNatural Killer Cellsen_US
dc.subjectRecombinase-Activating Genesen_US
dc.subjectNon-Homologous End Joiningen_US
dc.subjectImmunodeficiencyen_US
dc.subjectCd56en_US
dc.subjectInterferon-Gammaen_US
dc.subjectDegranulationen_US
dc.titleNatural Killer Cells from Patients with Recombinase-Activating Gene and Non-Homologous End Joining Gene Defects Comprise a Higher Frequency of CD56bright NKG2A+++ Cells, and Yet Display Increased Degranulation and Higher Perforin Contenten_US
dc.typeArticleen_US

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