DOCSLIB.ORG

Downloaded From

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Downloaded From Natural Killer Cell Development and Function Precede αβ T Cell Differentiation in Mouse Fetal Thymic Ontogeny This information is current as James R. Carlyle, Alison M. Michie, Sarah K. Cho and Juan of September 24, 2021. Carlos Zúñiga-Pflücker J Immunol 1998; 160:744-753; ; http://www.jimmunol.org/content/160/2/744 Downloaded from References This article cites 64 articles, 37 of which you can access for free at: http://www.jimmunol.org/content/160/2/744.full#ref-list-1 Why The JI? Submit online. http://www.jimmunol.org/ • 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 *average by guest on September 24, 2021 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 © 1998 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Natural Killer Cell Development and Function Precede ab T Cell Differentiation in Mouse Fetal Thymic Ontogeny1 James R. Carlyle, Alison M. Michie, Sarah K. Cho, and Juan Carlos Zu´n˜iga-Pflu¨cker2 Natural killer (NK) cells mediate MHC-unrestricted cytolysis of virus-infected cells and tumor cells. In the adult mouse, NK cells are bone marrow-derived lymphocytes that mature predominantly in extrathymic locations but have also been suggested to share a common intrathymic progenitor with T lymphocytes. However, mature NK cells are thought to be absent in mouse fetal ontogeny. We report the existence of thymocytes with a mature NK cell phenotype (NK1.11/CD1172) as early as day 13 of gestation, approximately 3 days before the appearance of CD41/CD81 cells in T lymphocyte development. These mature fetal thymic NK cells express genes associated with NK cell effector function and, when freshly isolated, display MHC-unrestricted cytolytic activity in vitro. Moreover, the capacity of fetal thymic NK cells for sustained growth both in vitro and in vivo, in addition to their close phenotypic resemblance to early precursor thymocytes, confounds previous assessments of NK lineage Downloaded from precursor function. Thus, mature NK cells may have been inadvertently included in previous attempts to identify multipotent and bipotent precursor thymocytes. These results provide the first evidence of functional NK lymphocytes in mouse fetal ontogeny and demonstrate that NK cell maturation precedes ab T cell development in the fetal thymus. The Journal of Immunology, 1998, 160: 744–753. igration of fetal liver-derived hemopoietic precursors pression of the winged-helix nude (whn) gene (10, 11). However, http://www.jimmunol.org/ to the early fetal thymic rudiment occurs by day 12 of the development of NK cells is thymus independent, and these mouse gestation. The earliest hemopoietic cells to col- cells are present at normal to elevated levels in athymic nude mice M 3 onize the thymus, thymic lymphoid progenitors (TLPs), are mul- as well as in mice defective in the ability to rearrange genes en- tipotent lymphoid-committed precursors capable of giving rise to coding the Ag receptors (severe combined immune deficiency the B, T, thymic dendritic, and NK cell lineages but lack signifi- (SCID) and RAG-deficient mice) (12–15). Nonetheless, in addi- cant potential for myeloid and other hemopoietic cells (1, 2). Soon tion to peripheral sites for NK lymphopoiesis, NK cell develop- after exposure to the thymic microenvironment, these precursors ment can occur within the thymus, and these cells have been sug- rapidly lose B lymphoid potential and become committed to the gested to share a common thymic progenitor with T lymphocytes by guest on September 24, 2021 T/NK lineages (3). Subsequently, a wave of thymocyte differen- within the TLP population (1, 2, 16–19). Previous studies pro- tiation is established in the fetal thymus, marked by the ordered vided evidence for, but failed to define, a proposed bipotent thymic appearance of various developmental stages along the pathway to progenitor for T and NK cells (16, 20–22); additionally, these mature T cells (1, 2, 4). In fetal thymic ontogeny, the development reports did not outline the earliest stages of NK cell development of a defined subset of gd T cells precedes that of conventional ab in fetal ontogeny. Instead, these investigations demonstrated that T cells (5). However, the ordered appearance of NK cells remains various purified populations of thymocytes can give rise to either unknown within the context of thymocyte development, and func- T or NK cells under different in vitro or in vivo conditions (16, tional NK cells are thought to be absent in mouse fetal ontogeny. 20–22). Importantly, none of these studies addressed the possibil- NK cells are responsible for mounting MHC-unrestricted cytol- ity that NK cells derived from populations of precursor thymo- ysis of virus-infected and transformed cells (6–9). The develop- cytes, upon i.v. injection or in vitro culture, represented an out- ment of mature peripheral ab and gd T cells is thymus-dependent growth of an already existent subset of mature NK cells. and does not occur efficiently in mice that fail to develop a proper To investigate these questions, we analyzed day 13 to 15 mouse thymic epithelium (nu/nu, or nude mice) due to a defect in ex- fetal thymocytes, which contain precursors for all lymphoid lin- eages, but no mature ab T or B lymphocytes, and have an overall CD32/CD42/CD82 triple-negative (TN) phenotype (1, 2, 4). Re- Department of Immunology, University of Toronto, Toronto, Ontario, Canada cently, we reported the identification of a novel population of thy- Received for publication August 27, 1997. Accepted for publication October mocytes that serve as common committed progenitors for T and 3, 1997. NK lymphocytes (3). These precursors display both the NK1.1 The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in molecule (NKR-P1C) of NK cells (23, 24) as well as the CD117 accordance with 18 U.S.C. Section 1734 solely to indicate this fact. (c-kit) molecule characteristic of hemopoietic precursors (17, 25– 1 1 This work was supported by grants from the Medical Research Council of Can- 27). We now report the identification of NK1.1 thymocytes with ada (MRC) and the National Cancer Institute of Canada (to J.C.Z.-P.), and by an a mature NK cell phenotype, lacking expression of CD117. These MRC studentship (to J.R.C) and an MRC scholarship (to J.C.Z.-P.). fetal thymic NK cells are evident as early as day 13 to 14 of 2 Address correspondence and reprint requests to Dr. J.C. Zu´n˜iga-Pflu¨cker, Depart- ment of Immunology, University of Toronto, Medical Sciences Building, Toronto, gestation, express genes associated with NK cell effector function, Ontario, M5S 1A8 Canada. E-mail address: jc.zuniga.pfl[email protected] and display MHC-unrestricted cytolytic activity directly ex vivo. 3 Abbreviations used in this paper: TLP, thymic lymphoid progenitor; FTLP, fetal Strikingly, despite the above functional characteristics and lack of TLP; FTNK: fetal thymic NK1.11 progenitor; FTOC: fetal thymic organ culture; CD117 surface expression, these mature NK cells possess a com- HSA: heat stable antigen; RAG: recombination-activating gene; SCF: stem cell posite phenotype similar to early precursor thymocytes, including factor; TN, triple negative; FT, fetal thymocytes; Sw, Swiss.NIH; dGuo, 1 2 1 deoxyguanosine. a CD44 (Pgp-1), CD25 (IL-2Ra), CD16/32 (FcgRIII/II), Copyright © 1998 by The American Association of Immunologists 0022-1767/98/$02.00 The Journal of Immunology 745 1 2 1 1 2 CD24low (HSA), CD90 / (Thy-1), CD122 (IL-2Rb), CD2 / GCA TAC AGG; NKR-P1 (genes 2, 34, 40) 59, AAG GTA CAC ATT (LFA-2), CD52 (Ly-1), and TN phenotype. Many of these char- GCC AGA CAT; NKR-P1A (gene 2) 39, GTA GAC ATG GCT CAG TGA 9 acteristics have been previously used in an attempt to define bi- TTG; NKR-P1B (gene 34) 3 , GGA CAG GGG AGA GAT GGA GAT; NKR-P1C (gene 40, NK1.1) 39, GAG TCA ACG AAT GGA AAG GAA; potent T/NK precursor cells as well as early T lineage precursors Ly-49A 59, TTC TGC TTC CTT CTT CTG GTA; Ly-49A 39, TGT GTT (16, 22). We now demonstrate directly that fetal thymic NK cells CAA GGC AAG TTT AGA; Ly-49C 59, AGA CCA GAA AAA CGC are capable of substantial growth, both in vitro and in vivo, con- CAA CTT; Ly-49C 39, TTC ACT GTT CCA TCT GTC CTG; perforin 59, tributing significantly to the NK cell reconstitution potential of ATG TTC CCC AGT CGT GAG AGG; perforin 39, AAG GTG GAG TGG AGG TTT TTG; CD95L (Fas-ligand) 59, AAG AGA ACA GGA GAA precursor-phenotype thymocytes upon adoptive transfer. Thus, NK ATG GTG; CD95L 39, AGA TTT GTG TTG TGG TCC TTC. cell progenitor activity reported in previous studies that failed to exclude fetal thymic NK cells may have stemmed from an out- 51Cr-release cell-mediated cytotoxicity assay growth of pre-existing mature NK cells, in addition to bona fide Single-cell suspensions from freshly isolated day 15 fetal thymocytes from NK cell precursor activity. These results indicate that the early timed-pregnant C57BL/6 mice and adult RAG-22/2 mice were sorted for 2 1 fetal thymus is completely capable of supporting NK lineage de- a CD3 /CD90 (Thy-1) phenotype with or without NK1.1 expression.
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]
  • 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 .
    [Show full text]