DOCSLIB.ORG

The Role of Natural Killer Cells in Parkinson's Disease

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Role of Natural Killer Cells in Parkinson's Disease Earls and Lee Experimental & Molecular Medicine (2020) 52:1517–1525 https://doi.org/10.1038/s12276-020-00505-7 Experimental & Molecular Medicine REVIEW ARTICLE Open Access The role of natural killer cells in Parkinson’s disease Rachael H. Earls1 and Jae-Kyung Lee 1 Abstract Numerous lines of evidence indicate an association between sustained inflammation and Parkinson’s disease, but whether increased inflammation is a cause or consequence of Parkinson’s disease remains highly contested. Extensive efforts have been made to characterize microglial function in Parkinson’s disease, but the role of peripheral immune cells is less understood. Natural killer cells are innate effector lymphocytes that primarily target and kill malignant cells. Recent scientific discoveries have unveiled numerous novel functions of natural killer cells, such as resolving inflammation, forming immunological memory, and modulating antigen-presenting cell function. Furthermore, natural killer cells are capable of homing to the central nervous system in neurological disorders that exhibit exacerbated inflammation and inhibit hyperactivated microglia. Recently, a study demonstrated that natural killer cells scavenge alpha-synuclein aggregates, the primary component of Lewy bodies, and systemic depletion of natural killer cells results in exacerbated neuropathology in a mouse model of alpha-synucleinopathy, making them a highly relevant cell type in Parkinson’s disease. However, the exact role of natural killer cells in Parkinson’s disease remains elusive. In this review, we introduce the systemic inflammatory process seen in Parkinson’s disease, with a particular focus on the direct and indirect modulatory capacity of natural killer cells in the context of Parkinson’s disease. 6,7 1234567890():,; 1234567890():,; 1234567890():,; 1234567890():,; Introduction dopaminergic (DA) neurons such as astrocytes . The Parkinson’s disease (PD) is the second most common exact cause of α-syn aggregation is debated, but the neurodegenerative disease that affects over one million importance of this protein in PD is highlighted through people in the United States, with predictable healthcare- genetic studies revealing missense, duplication, or tripli- associated costs of nearly $52 billion per year1.PDis cation mutations in the SNCA gene encoding α-syn pathologically characterized by the misfolding and leading to early-onset PD with prominent dementia8. aggregation of the alpha-synuclein (α-syn) protein into Importantly, human patient samples revealed aberrant α- insoluble inclusions known as Lewy bodies (LBs) and syn distribution peripherally within blood plasma9, Lewy neurites2. Monomeric α-syn protein is highly interstitial fluid10,11, and the enteric nervous system expressed in presynaptic terminals3 and the nucleus4 of (ENS)12, implicating prion-like replication and spreading cells. However, α-syn can acquire toxic properties through of α-syn. The accumulation of α-syn aggregates can pro- the pathogenic process of misfolding into α-syn fibrils that mote sustained activation of pattern-recognition recep- comprise the major component of LBs. LBs are present in tors (PRRs), leading to the production of proinflammatory PD, dementia with Lewy bodies (DLB), and Alzheimer’s cytokines in microglia13,14. These inflammatory mediators disease (AD) brains; however, each disease shows distinct from microglia and chemoattractant molecules from regional specificity, with PD patients displaying LBs most damaged neurons possibly play a role in infiltrating per- prominently in the substantia nigra (SN)5. Furthermore, ipheral cells into the central nervous system (CNS)15. in human sporadic PD cases and murine models of PD, Peripheral inflammation has been shown to exacerbate LB formation is present in numerous cell types other than DA neurodegeneration in numerous animal models of PD16,17. Extracellular α-syn aggregates may elicit a self- amplifying cycle of immune responses in the CNS14,18 and Correspondence: Jae-Kyung Lee ([email protected]) 19 1Department of Physiology and Pharmacology, University of Georgia College periphery through an overproduction of inflammatory of Veterinary Medicine, Athens, GA 30602, USA © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a linktotheCreativeCommons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Official journal of the Korean Society for Biochemistry and Molecular Biology Earls and Lee Experimental & Molecular Medicine (2020) 52:1517–1525 1518 mediators, thus providing the tertiary hit required for PD- transfer of α-syn is conducted via direct contact and associated dysfunction to spread to neighboring neurons tunneling nanotubes (TNTs)38. α-Syn is localized to the in the CNS20,21 and the periphery22. Therefore, lysosomal compartment of astrocytes and neurons; how- immunomodulatory-based approaches aimed at halting ever, a progressive increase in cleaved and full-length α- the propagation and burden of extracellular α-syn, and in syn was displayed in neurons over time, while astrocytes turn diminishing the inflammatory response, are currently displayed efficient degradation of α-syn37. However, fail- being tested as a therapeutic for PD and related synu- ure of the lysosomal digestion of excess α-syn oligomers cleinopathies (reviewed in23). Recently, it was discovered in astrocytes results in α-syn deposits in the trans-Golgi that natural killer (NK) cells efficiently internalize and network followed by endoplasmic reticulum swelling and degrade α-syn aggregates via the endosomal/lysosomal mitochondrial disturbances38. Moreover, exogenous α- pathway, a novel and highly relevant function of NK cells syn induced increased mRNA expression of proin- in synucleinopathies24. The number of circulating NK flammatory cytokines (IL-1β, TNF-α), iNOS, and cells in PD patients is increased compared to non-PD cyclooxygenase-2 (COX-2) from primary mouse astro- controls25. Furthermore, NK cells are present in the cytes in a TLR4-dependent manner39. human postmortem PD SN24 and PD mouse brain26, and Peripheral inflammation has been deemed a significant depletion of NK cells in a mouse model of synucleino- contributing factor in PD pathogenesis. Serum levels of pathies is associated with increased neuropathology24.In IL-1β, IL-2, IL-10, interferon-gamma (IFN-γ), and TNF-α this review, we review α-syn-associated immune respon- have been correlated with the severity of PD symp- ses, the potential role of NK cells, and the mechanisms by toms40,41 and rate of disease progression42. Serum auto- which NK cells exert their effects on PD pathogenesis. immune antibodies against α-syn are significantly elevated in PD patients43. Autoantibody titers, α-syn monomers, Implications of α-syn-associated immune and oligomers plus fibrils in 72%, 56%, and 17% of PD responses in PD patients are elevated, respectively, within a 5-year disease Although the etiology of PD is considered multifactorial duration44, which implicates systemic adaptive immune in nature, genetic studies have identified several loci responses against different α-syn species. PD patients also involved in inflammation, including the human leukocyte have a T helper cell 1 (Th1) bias in peripheral blood with antigen-DR isotype (HLA-DR), that lead to an increased naïve CD4+ T cells from patients preferentially differ- risk of PD27. It is hypothesized that misfolded α-syn may entiating to a Th1 proinflammatory lineage and showing potentiate the observed increase in inflammation seen in augmented production of IFN-γ and TNF-α45. Moreover, PD, as excessive aggregated α-syn can hyperactivate peripheral blood mononuclear cell (PBMC)-derived microglia18 and promote neurotoxic effects by enhancing CD4+ T cells from PD patients specifically react to the release of tumor necrosis factor-alpha (TNF-α), antigenic major histocompatibility class two (MHC-II) interleukin (IL) 1-beta (IL-1β), IL-6, nitric oxide (NO), epitopes derived from α-syn46, revealing T cell specificity inducible nitric oxide synthase (iNOS), and reactive oxy- to the α-syn antigen. Substantial increases in inflamma- gen species (ROS). Microglia phagocytose extracellular α- tory cytokines (IL-1β, TNF-α, IL-6)47 and intestinal per- – syn28 via various receptors, including Toll-like recep- meability48 50 are correlated with the presence of α-syn tors13,14. As microglia clear α-syn aggregates, they become aggregates within the gut51. Increased intestinal perme- activated independent of internalization and phagocy- ability is thought to result from reductions in barrier- tosis29,30. The distinct mechanisms of α-syn-induced promoting proteins and disruptions of tight-junction activation seem to be α-syn species-specific28. For exam- networks49, a phenotype consistent with low-grade ple, monomeric and mutant α-syn can bind to CD36 on inflammation52,53. microglia,
Load more

Recommended publications
  • One-Year Follow-Up of Natural Killer Cell Activity in Multiple Myeloma
    One-Year Follow-Up of Natural Killer Cell Activity in Multiple Myeloma Patients Treated With Adjuvant Lenalidomide Therapy Laurie Besson, Emily Charrier, Lionel Karlin, Omran Allatif, Antoine Marçais, Paul Rouzaire, Lucie Belmont, Michel Attal, Christine Lombard, Gilles Salles, et al. To cite this version: Laurie Besson, Emily Charrier, Lionel Karlin, Omran Allatif, Antoine Marçais, et al.. One- Year Follow-Up of Natural Killer Cell Activity in Multiple Myeloma Patients Treated With Adjuvant Lenalidomide Therapy. Frontiers in Immunology, Frontiers, 2018, 9, pp.704. 10.3389/fimmu.2018.00704. hal-01833354 HAL Id: hal-01833354 https://hal.archives-ouvertes.fr/hal-01833354 Submitted on 22 Oct 2018 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Distributed under a Creative Commons Attribution| 4.0 International License ORIGINAL RESEARCH published: 13 April 2018 doi: 10.3389/fimmu.2018.00704 One-Year Follow-Up of Natural Killer Cell Activity in Multiple Myeloma Patients Treated With Adjuvant Lenalidomide Therapy Laurie Besson1,2,3,4,5,6†, Emily Charrier1,2,3,4,5,6†,
    [Show full text]
  • Role for NK Cells Inflammatory Response Reveals a Critical A
    A Fatal Cytokine-Induced Systemic Inflammatory Response Reveals a Critical Role for NK Cells This information is current as William E. Carson, Haixin Yu, Julie Dierksheide, Klaus of September 28, 2021. Pfeffer, Page Bouchard, Reed Clark, Joan Durbin, Albert S. Baldwin, Jacques Peschon, Philip R. Johnson, George Ku, Heinz Baumann and Michael A. Caligiuri J Immunol 1999; 162:4943-4951; ; http://www.jimmunol.org/content/162/8/4943 Downloaded from References This article cites 61 articles, 37 of which you can access for free at: http://www.jimmunol.org/content/162/8/4943.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 28, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 1999 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. A Fatal Cytokine-Induced Systemic Inflammatory Response Reveals a Critical Role for NK Cells1 William E. Carson,2*† Haixin Yu,† Julie Dierksheide,‡ Klaus Pfeffer,§ Page Bouchard,¶ Reed Clark,| Joan Durbin,| Albert S.
    [Show full text]
  • High Mtor Activity Is a Hallmark of Reactive Natural Killer Cells And
    RESEARCH ARTICLE High mTOR activity is a hallmark of reactive natural killer cells and amplifies early signaling through activating receptors Antoine Marc¸ais1,2,3,4,5*, Marie Marotel1,2,3,4,5, Sophie Degouve1,2,3,4,5, Alice Koenig1,2,3,4,5, Se´ bastien Fauteux-Daniel1,2,3,4,5, Annabelle Drouillard1,2,3,4,5, Heinrich Schlums6, Se´ bastien Viel1,2,3,4,5,7, Laurie Besson1,2,3,4,5, Omran Allatif1,2,3,4,5, Mathieu Ble´ ry8, Eric Vivier9,10, Yenan Bryceson6,11, Olivier Thaunat1,2,3,4,5, Thierry Walzer1,2,3,4,5* 1CIRI, Centre International de Recherche en Infectiologie - International Center for Infectiology Research, Lyon, France; 2Inserm, U1111, Lyon, France; 3Ecole Normale Supe´rieure de Lyon, Lyon, France; 4Universite´ Lyon 1, Lyon, France; 5CNRS, UMR5308, Lyon, France; 6Centre for Hematology and Regenerative Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden; 7Laboratoire d’Immunologie, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Lyon, France; 8Innate-Pharma, Marseille, France; 9Aix-Marseille Universite´, CNRS, INSERM, CIML, Marseille, France; 10APHM, Hoˆpital de la Timone, Service d’Immunologie, Marseille, France; 11Broegelmann Research Laboratory, The Gades Institute, University of Bergen, Bergen, Norway Abstract NK cell education is the process through which chronic engagement of inhibitory NK *For correspondence: cell receptors by self MHC-I molecules preserves cellular responsiveness. The molecular [email protected] (AM); mechanisms responsible for NK cell education remain unclear. Here, we show that mouse NK cell [email protected] (TW) education is associated with a higher basal activity of the mTOR/Akt pathway, commensurate to Competing interest: See the number of educating receptors.
    [Show full text]
  • Natural Killer Cell: Repertoire Development, Education and Activation
    Zurich Open Repository and Archive University of Zurich Main Library Strickhofstrasse 39 CH-8057 Zurich www.zora.uzh.ch Year: 2016 Natural Killer Cell: Repertoire Development, Education and Activation Landtwing, Vanessa Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-136828 Dissertation Originally published at: Landtwing, Vanessa. Natural Killer Cell: Repertoire Development, Education and Activation. 2016, University of Zurich, Faculty of Science. Natural Killer Cell: Repertoire Development, Education and Activation Dissertation zur Erlangung der naturwissenschaftlichen Doktorwürde (Dr.sc.nat.) vorgelegt der Mathematisch-naturwissenschaftlichen Fakultät Der Universität Zürich von Vanessa Sonja Landtwing von Zug ZG Promotionskomitee Prof. Dr. Christian Münz (Vorsitz, Leitung der Dissertation) Prof. Dr. med. Markus Manz Prof. Dr. Werner Held Zürich, 2016 Table of Contents TABLE OF CONTENTS Abbreviations ................................................................................................................................. 1 Chapter One - General Summary .................................................................................. 3 1.1 Zusammenfassung ............................................................................................................................. 5 1.2 Summary ................................................................................................................................................ 7 Chapter Two - Introduction ..........................................................................................
    [Show full text]
  • Cytolytic Activity Cells Acquire Functional Receptors and Human Embryonic Stem Cell-Derived NK
    Human Embryonic Stem Cell-Derived NK Cells Acquire Functional Receptors and Cytolytic Activity This information is current as Petter S. Woll, Colin H. Martin, Jeffrey S. Miller and Dan S. of September 23, 2021. Kaufman J Immunol 2005; 175:5095-5103; ; doi: 10.4049/jimmunol.175.8.5095 http://www.jimmunol.org/content/175/8/5095 Downloaded from References This article cites 57 articles, 29 of which you can access for free at: http://www.jimmunol.org/content/175/8/5095.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 23, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2005 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Human Embryonic Stem Cell-Derived NK Cells Acquire Functional Receptors and Cytolytic Activity1 Petter S. Woll,* Colin H. Martin,* Jeffrey S. Miller,† and Dan S. Kaufman2* Human embryonic stem cells (hESCs) provide a unique resource to analyze early stages of human hematopoiesis.
    [Show full text]
  • Leukocytosis and Natural Killer Cell Function Parallel Neurobehavioral Fatigue Induced by 64 Hours of Sleep Deprivation
    Leukocytosis and natural killer cell function parallel neurobehavioral fatigue induced by 64 hours of sleep deprivation. D F Dinges, … , E Icaza, M T Orne J Clin Invest. 1994;93(5):1930-1939. https://doi.org/10.1172/JCI117184. Research Article The hypothesis that sleep deprivation depresses immune function was tested in 20 adults, selected on the basis of their normal blood chemistry, monitored in a laboratory for 7 d, and kept awake for 64 h. At 2200 h each day measurements were taken of total leukocytes (WBC), monocytes, granulocytes, lymphocytes, eosinophils, erythrocytes (RBC), B and T lymphocyte subsets, activated T cells, and natural killer (NK) subpopulations (CD56/CD8 dual-positive cells, CD16- positive cells, CD57-positive cells). Functional tests included NK cytotoxicity, lymphocyte stimulation with mitogens, and DNA analysis of cell cycle. Sleep loss was associated with leukocytosis and increased NK cell activity. At the maximum sleep deprivation, increases were observed in counts of WBC, granulocytes, monocytes, NK activity, and the proportion of lymphocytes in the S phase of the cell cycle. Changes in monocyte counts correlated with changes in other immune parameters. Counts of CD4, CD16, CD56, and CD57 lymphocytes declined after one night without sleep, whereas CD56 and CD57 counts increased after two nights. No changes were observed in other lymphocyte counts, in proliferative responses to mitogens, or in plasma levels of cortisol or adrenocorticotropin hormone. The physiologic leukocytosis and NK activity increases during deprivation were eliminated by recovery sleep in a manner parallel to neurobehavioral function, suggesting that the immune alterations may be associated with biological pressure for sleep.
    [Show full text]
  • Restoring Natural Killer Cell Immunity Against Multiple Myeloma in the Era of New Drugs
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Institutional Research Information System University of Turin Restoring Natural Killer Cell immunity against Multiple Myeloma in the era of New Drugs Gianfranco Pittari1, Luca Vago2,3, Moreno Festuccia4,5, Chiara Bonini6,7, Deena Mudawi1, Luisa Giaccone4,5 and Benedetto Bruno4,5* 1 Department of Medical Oncology, National Center for Cancer Care and Research, HMC, Doha, Qatar, 2 Unit of Immunogenetics, Leukemia Genomics and Immunobiology, IRCCS San Raffaele Scientific Institute, Milano, Italy, 3 Hematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milano, Italy, 4 Department of Oncology/Hematology, A.O.U. Città della Salute e della Scienza di Torino, Presidio Molinette, Torino, Italy, 5 Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy, 6 Experimental Hematology Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milano, Italy, 7 Vita-Salute San Raffaele University, Milano, Italy Transformed plasma cells in multiple myeloma (MM) are susceptible to natural killer (NK) cell-mediated killing via engagement of tumor ligands for NK activating receptors or “missing-self” recognition. Similar to other cancers, MM targets may elude NK cell immunosurveillance by reprogramming tumor microenvironment and editing cell surface antigen repertoire. Along disease continuum, these effects collectively result in a pro- gressive decline of NK cell immunity, a phenomenon increasingly recognized as a critical determinant of MM progression. In recent years, unprecedented efforts in drug devel- opment and experimental research have brought about emergence of novel therapeutic interventions with the potential to override MM-induced NK cell immunosuppression.
    [Show full text]
  • Natural Killer Cell Immunosuppressive Function Requires CXCR3-Dependent Redistribution Within Lymphoid Tissues
    bioRxiv preprint doi: https://doi.org/10.1101/2021.05.11.443590; this version posted May 11, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Natural killer cell immunosuppressive function requires CXCR3- dependent redistribution within lymphoid tissues Ayad Ali1,2,3, Laura M. Canaday2,3, H. Alex Feldman1,2,3, Hilal Cevik3,4, Michael T. Moran2,3, Sanjeeth Rajaram3,5, Nora Lakes1,2, Jasmine A. Tuazon3, Harsha Seelamneni3, Durga Krishnamurthy3, Eryn Blass6, Dan H. Barouch6,7, Stephen N. Waggoner1,2,3,4,8,* 1Medical Scientist Training Program, 2Immunology Graduate Training Program, 4Molecular and Developmental Biology Graduate Program, 5Medical Sciences Program, 8Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 3Center for Autoimmune Genomics and Etiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 6Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 7Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA *E-mail: [email protected] Natural killer (NK) cell suppression of T cells is a key determinant of viral pathogenesis and vaccine efficacy. This process involves perforin-dependent elimination of activated CD4 T cells during the first three days of infection. Although this mechanism requires cell-cell contact, NK cells and T cells typically reside in different compartments of lymphoid tissues at steady state. Here, we show that NK-cell suppression of T cells is associated with a transient accumulation of NK cells within T cell-rich sites of the spleen during lymphocytic choriomeningitis virus infection.
    [Show full text]
  • Regulation of Hematopoiesis in Vitro by Alloreactive Natural Killer Cell Clones by Graziella Beuone,*~ Nicholas M. Valiante,* Oriane Viale, S
    Regulation of Hematopoiesis In Vitro by Alloreactive Natural Killer Cell Clones By Graziella BeUone,*~ Nicholas M. Valiante,* Oriane Viale,S Ermanno Ciccone,S Lorenzo Moretta,$ and Giorgio Trinchieri* From "The Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania 19104; the ~Istituto di Medicina Interna, 10126 Torino; and the $Istituto Nazionale per la Ricerca sul Cancro, 16132 Genova, Italy Slllllrlm~ Natural killer (NK) ceils lyse autologous and allogeneic target cells even in the absence of major histocompatibility complex (MHC) dass I antigens on the target cells. Recently, however, human allospecific NK cell clones have been generated that recognize at least five distinct specificities inherited recessively and controlled by genes linked to the MHC. Because the genetic specificity of these alloreactive NK cells in vitro appears analogous to that of in vivo NK cell-mediated murine hybrid resistance, i.e., the rejection of parental bone marrow in irradiated F1 animals, we tested the ability of human aUoreactive NK clones to recognize allogeneic hematopoietic progenitor cells. NK cells from two specificity 1 alloreactive NK clones, ES9 and ES10, significantly and often completely suppressed colony formation by purified peripheral blood hematopoietic progenitor ceils from specificity 1-susceptible donors, but had no significant effect on the cells of specificity 1-resistant donors. Activated polyclonal NK cells were less efficient than the NK clones in inhibiting colony formation and had a similar effect on cells from both specificity 1-susceptible and -resistant donors. The alloreactive NK clones produced cytokines with a suppressive effect on in vitro hematopoiesis, such as interferon 3, (IFN-'y) and tumor necrosis factor oe (TNF-o 0, when exposed to phytohemagglutinin blasts from specificity 1-susceptible, but not -resistant donors.
    [Show full text]
  • Conditioning Regimens for Autologous Haematopoietic Stem Cell Transplantation - Can Natural Killer Cell Therapy Help?
    This is a repository copy of Conditioning regimens for autologous haematopoietic stem cell transplantation - can natural killer cell therapy help?. White Rose Research Online URL for this paper: http://eprints.whiterose.ac.uk/114154/ Version: Accepted Version Article: Snowden, J.A. and Hill, G.R. (2017) Conditioning regimens for autologous haematopoietic stem cell transplantation - can natural killer cell therapy help? British Journal of Haematology. ISSN 0007-1048 https://doi.org/10.1111/bjh.14565 This is the peer reviewed version of the following article: Snowden, J. A. and Hill, G. R. (2017), Conditioning regimens for autologous haematopoietic stem cell transplantation – can natural killer cell therapy help?. Br J Haematol. , which has been published in final form at https://doi.org/doi:10.1111/bjh.14565. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. Reuse Unless indicated otherwise, fulltext items are protected by copyright with all rights reserved. The copyright exception in section 29 of the Copyright, Designs and Patents Act 1988 allows the making of a single copy solely for the purpose of non-commercial research or private study within the limits of fair dealing. The publisher or other rights-holder may allow further reproduction and re-use of this version - refer to the White Rose Research Online record for this item. Where records identify the publisher as the copyright holder, users can verify any specific terms of use on the publisher’s website. Takedown If you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing [email protected] including the URL of the record and the reason for the withdrawal request.
    [Show full text]
  • Human NK Cells in Autologous Hematopoietic Stem Cell Transplantation for Cancer Treatment
    cancers Review Human NK Cells in Autologous Hematopoietic Stem Cell Transplantation for Cancer Treatment Ane Orrantia 1 , Iñigo Terrén 1 , Gabirel Astarloa-Pando 1, Olatz Zenarruzabeitia 1,* and Francisco Borrego 1,2,* 1 Immunopathology Group, Biocruces Bizkaia Health Research Institute, 48903 Barakaldo, Spain; [email protected] (A.O.); [email protected] (I.T.); [email protected] (G.A.-P.) 2 Ikerbasque, Basque Foundation for Science, 48013 Bilbao, Spain * Correspondence: [email protected] (O.Z.); [email protected] (F.B.); Tel.: +34-94-600-6000 (ext. 2402) (O.Z.); +34-94-600-6000 (ext. 7079) (F.B.) Simple Summary: Natural killer (NK) cells are key elements of the innate immune system that have the ability to kill transformed (tumor and virus-infected) cells without prior sensitization. Hematopoietic stem cell transplantation (HSCT) is a medical procedure used in the treatment of a variety of cancers. The early reconstitution of NK cells after HSCT and their functions support the therapeutic potential of these cells in allogenic HSCT. However, the role of NK cells in autologous HSCT is less clear. In this review, we have summarized general aspects of NK cell biology. In addition, we have also reviewed factors that affect autologous HSCT outcome, with particular attention to the role played by NK cells. Citation: Orrantia, A.; Terrén, I.; Abstract: Natural killer (NK) cells are phenotypically and functionally diverse lymphocytes with Astarloa-Pando, G.; Zenarruzabeitia, the ability to recognize and kill malignant cells without prior sensitization, and therefore, they have O.; Borrego, F. Human NK Cells in Autologous Hematopoietic Stem Cell a relevant role in tumor immunosurveillance.
    [Show full text]
  • Developmental Pathways That Generate Natural-Killer-Cell Diversity in Mice and Humans
    REVIEWS Developmental pathways that generate natural-killer-cell diversity in mice and humans Nicholas D. Huntington, Christian A. J. Vosshenrich and James P. Di Santo Abstract | Natural killer (NK) cells are large granular lymphocytes capable of producing inflammatory cytokines and spontaneously killing malignant, infected or ‘stressed’ cells. These NK-cell functions are controlled by cell-surface receptors that titrate stimulatory and inhibitory signals. However, we remain puzzled about where and when NK cells develop and differentiate, and this has fuelled the debate over the diversification of the peripheral NK-cell pool: are NK cells functionally homogeneous or are there subsets with specialized effector functions? In this Review, we consider the developmental relationships and biological significance of the diverse NK-cell subsets in mice and humans, and discuss how new humanized mouse models may help to characterize them further. Natural killer (NK) cells are a subset of lymphocytes transcription) so that they are capable of a ‘one cell does that principally participate in innate immunity but all’ endpoint but that at the same time are still able to may also have important roles in determining the generate adequate effector functions under diverse outcome of the adaptive immune responses. Diverse assaults might prove difficult. So, rather than by having a functional activities have been associated with NK single multifunctional cell, diverse NK‑cell effector func- cells, including ‘natural’ (immediate) cytotoxic- tions could be achieved in an alternative way through ity and the capacity to promptly produce cytokines NK‑cell diversification. In this way, the functional pleio­ (tumour-necrosis factor (TNF) and interferon‑γ tropy exhibited by NK cells during immune responses (IFNγ)) and chemokines that help to generate and would be governed by distinct NK‑cell subsets.
    [Show full text]