ArticleThe Journal of clinical investigation2016
Cognate HLA absence in trans diminishes human NK cell education.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
28 citing papers in PubMed, 37 citations in OpenAlex.
- Review
- Humanized Mouse Models of Epstein Barr Virus Infection.Current protocols · 2025Article
- Enhanced development of functional human NK cells in NOD-scid-IL2rgFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Review
- Prophylactic and Therapeutic EBV Vaccines: Major Scientific Obstacles, Historical Progress, and Future Direction.Vaccines · 2021Review
- Review
- Review
- KSHV infection drives poorly cytotoxic CD56-negative natural killer cell differentiation in vivo upon KSHV/EBV dual infection.Cell reports · 2021Article
- The Role of Lytic Infection for Lymphomagenesis of Human γ-Herpesviruses.Frontiers in cellular and infection microbiology · 2021Review
- Modification of EBV-Associated Pathologies and Immune Control by Coinfections.Frontiers in oncology · 2021Review
- Modification of EBV Associated Lymphomagenesis and Its Immune Control by Co-Infections and Genetics in Humanized Mice.Frontiers in immunology · 2021Review
- Review
- Immunosuppressive FK506 treatment leads to more frequent EBV-associated lymphoproliferative disease in humanized mice.PLoS pathogens · 2020Article
- Probing Reconstituted Human Immune Systems in Mice With Oncogenic γ-Herpesvirus Infections.Frontiers in immunology · 2020Review
- Decreased iKIR-HLA C Pair Confers Worse Clinical Outcomes for Patients With Myeloid Disease Receiving Antithymocyte Globulin-Based Haploidentical Hematopoietic Stem Cell Transplantation.Frontiers in immunology · 2020Article
- Review
- Infection and immune control of human oncogenic γ-herpesviruses in humanized mice.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2019Review
- Plasmacytoid dendritic cells respond to Epstein-Barr virus infection with a distinct type I interferon subtype profile.Blood advances · 2019Article
- Immunodeficiencies that predispose to pathologies by human oncogenic γ-herpesviruses.FEMS microbiology reviews · 2019Review
- Remodeling of secretory lysosomes during education tunes functional potential in NK cells.Nature communications · 2019Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 7 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
NK cells are innate lymphocytes with protective functions against viral infections and tumor formation. Human NK cells carry inhibitory killer cell Ig-like receptors (KIRs), which recognize distinct HLAs. NK cells with KIRs for self-HLA molecules acquire superior cytotoxicity against HLA- tumor cells during education for improved missing-self recognition. Here, we reconstituted mice with human hematopoietic cells from donors with homozygous KIR ligands or with a mix of hematopoietic cells from these homozygous donors, allowing assessment of the resulting KIR repertoire and NK cell education. We found that co-reconstitution with 2 KIR ligand-mismatched compartments did not alter the frequency of KIR-expressing NK cells. However, NK cell education was diminished in mice reconstituted with parallel HLA compartments due to a lack of cognate HLA molecules on leukocytes for the corresponding KIRs. This change in NK cell education in mixed human donor-reconstituted mice improved NK cell-mediated immune control of EBV infection, indicating that mixed hematopoietic cell populations could be exploited to improve NK cell reactivity against leukotropic pathogens. Taken together, these findings indicate that leukocytes lacking cognate HLA ligands can disarm KIR+ NK cells in a manner that may decrease HLA- tumor cell recognition but allows for improved NK cell-mediated immune control of a human γ-herpesvirus.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.