DOCSLIB.ORG

Early KLRG1+ but Not CD57+CD8+ T Cells in Primary Cytomegalovirus Infection Predict Effector Function and Viral Control

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Early KLRG1+ but Not CD57+CD8+ T Cells in Primary Cytomegalovirus Infection Predict Effector Function and Viral Control Early KLRG1+ but Not CD57+CD8+ T Cells in Primary Cytomegalovirus Infection Predict Effector Function and Viral Control This information is current as Aki Hoji, Iulia D. Popescu, Matthew R. Pipeling, Pali D. of September 25, 2021. Shah, Spencer A. Winters and John F. McDyer J Immunol published online 25 September 2019 http://www.jimmunol.org/content/early/2019/09/19/jimmun ol.1900399 Downloaded from Supplementary http://www.jimmunol.org/content/suppl/2019/09/20/jimmunol.190039 Material 9.DCSupplemental 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 25, 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 © 2019 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Published September 25, 2019, doi:10.4049/jimmunol.1900399 The Journal of Immunology Early KLRG1+ but Not CD57+CD8+ T Cells in Primary Cytomegalovirus Infection Predict Effector Function and Viral Control Aki Hoji,*,1 Iulia D. Popescu,*,1 Matthew R. Pipeling,* Pali D. Shah,† Spencer A. Winters,* and John F. McDyer* CMV remains an important opportunistic pathogen in high-risk lung transplant recipients. We characterized the phenotype and function of CD8+ T cells from acute/primary into chronic CMV infection in 23 (donor+/recipient2; D+R2) lung transplant recipients and found rapid induction of both KLRG1+ and/or CD57+ CMV-specific CD8+ T cells with unexpected coexpression of CD27. These cells demonstrated maturation from an acute effector T cell (TAEFF) to an effector memory T cell (TEM) phenotype + + 2 + with progressive enrichment of KLRG1 CD57 CD27 cells into memory. CMV-specific KLRG1 TAEFF were capable of Downloaded from in vitro proliferation that diminished upon acquisition of CD57, whereas only KLRG1+ expression correlated with T-bet expression and effector function. In contrast to blood TAEFF, lung mucosal TAEFF demonstrated reduced KLRG1/T-bet expres- + sion but similar CD57 levels. Additionally, increased KLRG1 TAEFF were associated with early immune viral control following primary infection. To our knowledge, our findings provide new insights into the roles of KLRG1 and CD57 expression in human T cells, forming the basis for a refined model of CD8+ T cell differentiation during CMV infection. The Journal of Immunology, 2019, 203: 000–000. http://www.jimmunol.org/ ytomegalovirus, a member of the b-herpesvirus family, antiviral prophylaxis strategies in the past decade in many transplant remains a significant opportunistic pathogen and cause of programs, D+R2 LTRs (6), which compose 25% of all LTRs, C morbidity and mortality in solid organ and hematopoietic continue to demonstrate increased risk for recurrent CMV viremia cell transplant recipients. Lung transplant recipients (LTRs), in and CMV end-organ disease and increased 5-year mortality (7). We particular seronegative recipients of allografts from seropositive have previously demonstrated heterogeneity of CMV-specific T cell donors (donor+/recipient2;D+R2), are at increased risk for CMV immunity among the D+R2 LTR population that is predictive of complications (1, 2). CMV infectious complications such as the capacity for early viral control following primary infection. pneumonitis and viremia have been implicated in LTRs as risk Specifically, we have shown important roles for induction of the by guest on September 25, 2021 factors for developing chronic lung allograft dysfunction and the major type-1 transcription factor T-bet, effector function, and pro- bronchiolitis obliterans syndrome, the major limiting factor for liferative capacity in CD8+ and CD4+ T cells as significant func- long-term survival in LTRs (3–5). Despite the adoption of extended tional immune correlates for establishing viral control during early chronic CMV infection (8–10). Recently, we showed that idiopathic pulmonary fibrosis lung recipients with short telomeres demonstrate *Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Med- impaired CMV-specific T cell immunity and T-bet induction that icine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213; and correlated with increased risk for CMV complications (11). How- †Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205 ever, questions remain as to the optimal T cell marker(s) that could prospectively stratify high-risk lung recipients who are at risk for 1A.H. and I.D.P. contributed equally to this work. relapsing CMV following discontinuation of antiviral therapy ver- ORCIDs: 0000-0001-7093-3437 (A.H.); 0000-0003-4294-1223 (I.D.P.); 0000-0003- 0595-595X (J.F.M.). sus those with the capacity to establish immune control. Lung Received for publication April 5, 2019. Accepted for publication July 31, 2019. transplantation provides a unique opportunity to evaluate viral im- mune mechanisms, as the advent of primary CMV infection is often This work was supported by National Institutes of Health Grants R01 AI079175 and R01HL133184 (to J.F.M.) and funding from the Immune Transplant and Therapy known and both peripheral and allograft-derived resident T cells can Center of UPMC. be tracked into chronic infection (12, 13). A.H., I.D.P., and J.F.M. designed and analyzed experiments. A.H. and I.D.P. performed Similar to virus-specific CD8+ T cells in the mouse, a linear experiments and analyzed and interpreted results. A.H. wrote a majority of the manu- progression in differentiation is the current paradigm in human script, and I.D.P. contributed figure legends and methods. M.R.P. and P.D.S. provided clinical specimens and patients’ characteristics. I.D.P. and S.A.W. compiled patient data. T cells (14–16). However, although the phenotype and function of J.F.M. supervised the study and edited the manuscript. effector memory CMV-specific CD8+ T cells during chronic infec- Address correspondence and reprint requests to Dr. John F. McDyer, Division of tion has been widely investigated, the phenotypic correlates of CD8+ Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School T cells effector function during acute/primary CMV infection have of Medicine, 3459 Fifth Avenue, NW 628, Pittsburgh, PA 15213. E-mail address: [email protected] been less characterized. Early studies showed that CMV-specific + The online version of this article contains supplemental material. CD8 T cells during chronic infection are enriched predom- Abbreviations used in this article: BAL, bronchoalveolar lavage; ChIP, chromatin inantly in the mature effector memory T cell (TEM) phenotype 2 2 hi immunoprecipitation; D+R2, donor+/recipient2; KLRG1, killer cell lectin-like re- CD27 CD28 CD45RA , marked by the increased expression of ceptor subfamily G member 1; LMNC, lung mucosal mononuclear cell; LTR, lung granzymes A/B, perforin, and IFN-g but a diminished proliferative transplant recipient; T , acute effector T cell; T , effector memory T cell. AEFF EM capacity (17–19). In parallel, these cells acquire surface expression Copyright Ó 2019 by The American Association of Immunologists, Inc. 0022-1767/19/$37.50 of the terminal differentiation markers, coinhibitory receptor killer www.jimmunol.org/cgi/doi/10.4049/jimmunol.1900399 2 CMV KLRG1+CD8+ T CELLS PREDICT FUNCTION AND VIRAL CONTROL cell lectin-like receptor subfamily G member 1 (KLRG1) (20) and (time point referred to as “primary CMV”). PBMCs were isolated from CD57 (21, 22). Acquisition of CD57 expression is thought to occur heparinized blood samples by density gradient centrifugation using Ficoll- increasingly over the course of chronic CMV infection (16, 23), Paque (GE Healthcare) to be used in subsequent assays. Study participants underwent BAL by use of a standard protocol with instillation of 180 ml of whereas persistence of CMV Ag is thought to drive progressive sterile normal saline in the right middle lobe of the lung. A BAL speci- downregulation of CD27 into the TEM phase (24). men was obtained on the same day for blood collection. Lung mucosal In the acute/primary LCMV mouse infection model, KLRG1hi mononuclear cells (LMNCs) were obtained simply via centrifugation of surface expression marks short-lived effector cells that are critical BAL fluid. All patients had therapeutic levels of calcineurin inhibitors at for rapid viral clearance, and its expression is T-bet dependent the time of sampling. Cells were then washed with PBS, aliquoted at 10 million cells in 1 ml of freezing medium (Invitrogen), and frozen in (25). Although both KLRG1 and CD57 (no mouse equivalent) are the liquid nitrogen tank. PBMCs were thawed rapidly in the presence of + expressed in human memory CD8 T cells (26), and most notably 2 U per ml of Benzonase (EMD Millipore). in CMV-specific CD8+ T cells (27, 28), expression and potential MHC class I dextramer and surface staining of PBMCs functional correlation of these markers of terminal differentia- and LMNCs tion have not been evaluated during acute/primary viral infection. Based on our previous findings showing early T-bet induction in Cryopreserved PBMCs and LMNCs were thawed in in the presence of ∼ 3 6 CD8+ T cells during acute/primary CMV infection and its im- 2 U/ml Benzonase (EMD Millipore), and 2 10 cells were labeled with FV-510 (BD Biosciences) in IMDM medium (Life Technologies) for portance in viral control (8, 9), we hypothesized that an early + 10 min at 37˚C.
Load more

Recommended publications
  • List of Genes Used in Cell Type Enrichment Analysis
    List of genes used in cell type enrichment analysis Metagene Cell type Immunity ADAM28 Activated B cell Adaptive CD180 Activated B cell Adaptive CD79B Activated B cell Adaptive BLK Activated B cell Adaptive CD19 Activated B cell Adaptive MS4A1 Activated B cell Adaptive TNFRSF17 Activated B cell Adaptive IGHM Activated B cell Adaptive GNG7 Activated B cell Adaptive MICAL3 Activated B cell Adaptive SPIB Activated B cell Adaptive HLA-DOB Activated B cell Adaptive IGKC Activated B cell Adaptive PNOC Activated B cell Adaptive FCRL2 Activated B cell Adaptive BACH2 Activated B cell Adaptive CR2 Activated B cell Adaptive TCL1A Activated B cell Adaptive AKNA Activated B cell Adaptive ARHGAP25 Activated B cell Adaptive CCL21 Activated B cell Adaptive CD27 Activated B cell Adaptive CD38 Activated B cell Adaptive CLEC17A Activated B cell Adaptive CLEC9A Activated B cell Adaptive CLECL1 Activated B cell Adaptive AIM2 Activated CD4 T cell Adaptive BIRC3 Activated CD4 T cell Adaptive BRIP1 Activated CD4 T cell Adaptive CCL20 Activated CD4 T cell Adaptive CCL4 Activated CD4 T cell Adaptive CCL5 Activated CD4 T cell Adaptive CCNB1 Activated CD4 T cell Adaptive CCR7 Activated CD4 T cell Adaptive DUSP2 Activated CD4 T cell Adaptive ESCO2 Activated CD4 T cell Adaptive ETS1 Activated CD4 T cell Adaptive EXO1 Activated CD4 T cell Adaptive EXOC6 Activated CD4 T cell Adaptive IARS Activated CD4 T cell Adaptive ITK Activated CD4 T cell Adaptive KIF11 Activated CD4 T cell Adaptive KNTC1 Activated CD4 T cell Adaptive NUF2 Activated CD4 T cell Adaptive PRC1 Activated
    [Show full text]
  • Markers of T Cell Senescence in Humans
    International Journal of Molecular Sciences Review Markers of T Cell Senescence in Humans Weili Xu 1,2 and Anis Larbi 1,2,3,4,5,* 1 Biology of Aging Program and Immunomonitoring Platform, Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR), Immunos Building, Biopolis, Singapore 138648, Singapore; [email protected] 2 School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore 3 Department of Microbiology, National University of Singapore, Singapore 117597, Singapore 4 Department of Geriatrics, Faculty of Medicine, University of Sherbrooke, Sherbrooke, QC J1K 2R1, Canada 5 Faculty of Sciences, University ElManar, Tunis 1068, Tunisia * Correspondence: [email protected]; Tel.: +65-6407-0412 Received: 31 May 2017; Accepted: 26 July 2017; Published: 10 August 2017 Abstract: Many countries are facing the aging of their population, and many more will face a similar obstacle in the near future, which could be a burden to many healthcare systems. Increased susceptibility to infections, cardiovascular and neurodegenerative disease, cancer as well as reduced efficacy of vaccination are important matters for researchers in the field of aging. As older adults show higher prevalence for a variety of diseases, this also implies higher risk of complications, including nosocomial infections, slower recovery and sequels that may reduce the autonomy and overall quality of life of older adults. The age-related effects on the immune system termed as “immunosenescence” can be exemplified by the reported hypo-responsiveness to influenza vaccination of the elderly. T cells, which belong to the adaptive arm of the immune system, have been extensively studied and the knowledge gathered enables a better understanding of how the immune system may be affected after acute/chronic infections and how this matters in the long run.
    [Show full text]
  • Human Β‑1,3‑Glucuronyltransferase 1/B3GAT1 Antibody Monoclonal Mouse Igg2a Clone # 1002707 Catalog Number: MAB8560
    Human β‑1,3‑Glucuronyltransferase 1/B3GAT1 Antibody Monoclonal Mouse IgG2A Clone # 1002707 Catalog Number: MAB8560 DESCRIPTION Species Reactivity Human Specificity Detects human β-1,3-Glucuronyltransferase 1/B3GAT1 in direct ELISAs. Source Monoclonal Mouse IgG2A Clone # 1002707 Purification Protein A or G purified from hybridoma culture supernatant Immunogen Chinese Hamster Ovary cell line, CHO-derived human β‑1,3‑Glucuronyltransferase 1/B3GAT1 His25-Ile334 Accession # Q9P2W7 Formulation Lyophilized from a 0.2 μm filtered solution in PBS with Trehalose. See Certificate of Analysis for details. *Small pack size (-SP) is supplied either lyophilized or as a 0.2 μm filtered solution in PBS. APPLICATIONS Please Note: Optimal dilutions should be determined by each laboratory for each application. General Protocols are available in the Technical Information section on our website. Recommended Sample Concentration Immunohistochemistry 5-25 µg/mL See Below DATA Immunohistochemistry β-1,3-Glucuronyltransferase 1/B3GAT1 in Human Brain. β-1,3-Glucuronyltransferase 1/B3GAT1 was detected in immersion fixed paraffin-embedded sections of human brain (cortex) using Mouse Anti-Human β-1,3- Glucuronyltransferase 1/B3GAT1 Monoclonal Antibody (Catalog # MAB8560) at 5 µg/mL for 1 hour at room temperature followed by incubation with the Anti-Mouse IgG VisUCyte™ HRP Polymer Antibody (Catalog # VC001). Before incubation with the primary antibody, tissue was subjected to heat-induced epitope retrieval using Antigen Retrieval Reagent-Basic (Catalog # CTS013). Tissue was stained using DAB (brown) and counterstained with hematoxylin (blue). Specific staining was localized to cytoplasm in neurons. View our protocol for IHC Staining with VisUCyte HRP Polymer Detection Reagents. PREPARATION AND STORAGE Reconstitution Reconstitute at 0.5 mg/mL in sterile PBS.
    [Show full text]
  • CD38, CD157, and RAGE As Molecular Determinants for Social Behavior
    cells Review CD38, CD157, and RAGE as Molecular Determinants for Social Behavior Haruhiro Higashida 1,2,* , Minako Hashii 1,3, Yukie Tanaka 4, Shigeru Matsukawa 5, Yoshihiro Higuchi 6, Ryosuke Gabata 1, Makoto Tsubomoto 1, Noriko Seishima 1, Mitsuyo Teramachi 1, Taiki Kamijima 1, Tsuyoshi Hattori 7, Osamu Hori 7 , Chiharu Tsuji 1, Stanislav M. Cherepanov 1 , Anna A. Shabalova 1, Maria Gerasimenko 1, Kana Minami 1, Shigeru Yokoyama 1, Sei-ichi Munesue 8, Ai Harashima 8, Yasuhiko Yamamoto 8, Alla B. Salmina 1,2 and Olga Lopatina 2 1 Department of Basic Research on Social Recognition and Memory, Research Center for Child Mental Development, Kanazawa University, Kanazawa 920-8640, Japan; [email protected] (M.H.); [email protected] (R.G.); [email protected] (M.T.); [email protected] (N.S.); [email protected] (M.T.); [email protected] (T.K.); [email protected] (C.T.); [email protected] (S.M.C.); [email protected] (A.A.S.); [email protected] (M.G.); minami-k@staff.kanazawa-u.ac.jp (K.M.); [email protected] (S.Y.) 2 Laboratory of Social Brain Study, Research Institute of Molecular Medicine and Pathobiochemistry, Krasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky, Krasnoyarsk 660022, Russia; [email protected] (A.B.S.); [email protected] (O.L.) 3 Division of Molecular Genetics and Clinical Research, National Hospital Organization Nanao Hospital, Nanao 926-0841, Japan 4 Molecular Biology and Chemistry, Faculty of Medical Science, University of Fukui, Fukui
    [Show full text]
  • Dysregulated CD38 Expression on Peripheral Blood Immune Cell Subsets in SLE
    International Journal of Molecular Sciences Article Dysregulated CD38 Expression on Peripheral Blood Immune Cell Subsets in SLE Marie Burns 1,†, Lennard Ostendorf 1,2,3,† , Robert Biesen 1,2 , Andreas Grützkau 1, Falk Hiepe 1,2, Henrik E. Mei 1,† and Tobias Alexander 1,2,*,† 1 Deutsches Rheuma-Forschungszentrum (DRFZ Berlin), a Leibniz Institute, 10117 Berlin, Germany; [email protected] (M.B.); [email protected] (L.O.); [email protected] (R.B.); [email protected] (A.G.); [email protected] (F.H.); [email protected] (H.E.M.) 2 Department of Rheumatology and Clinical Immunology, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and The Berlin Institute of Health (BIH), 10117 Berlin, Germany 3 Department of Nephrology and Intensive Care Medicine, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and The Berlin Institute of Health (BIH), 10117 Berlin, Germany * Correspondence: [email protected] † Authors contributed equally to this manuscript. Abstract: Given its uniformly high expression on plasma cells, CD38 has been considered as a therapeutic target in patients with systemic lupus erythematosus (SLE). Herein, we investigate the distribution of CD38 expression by peripheral blood leukocyte lineages to evaluate the potential therapeutic effect of CD38-targeting antibodies on these immune cell subsets and to delineate the use of CD38 as a biomarker in SLE. We analyzed the expression of CD38 on peripheral blood leukocyte subsets by flow and mass cytometry in two different cohorts, comprising a total of 56 SLE patients. The CD38 expression levels were subsequently correlated across immune cell lineages and subsets, Citation: Burns, M.; Ostendorf, L.; and with clinical and serologic disease parameters of SLE.
    [Show full text]
  • CD Markers Are Routinely Used for the Immunophenotyping of Cells
    ptglab.com 1 CD MARKER ANTIBODIES www.ptglab.com Introduction The cluster of differentiation (abbreviated as CD) is a protocol used for the identification and investigation of cell surface molecules. So-called CD markers are routinely used for the immunophenotyping of cells. Despite this use, they are not limited to roles in the immune system and perform a variety of roles in cell differentiation, adhesion, migration, blood clotting, gamete fertilization, amino acid transport and apoptosis, among many others. As such, Proteintech’s mini catalog featuring its antibodies targeting CD markers is applicable to a wide range of research disciplines. PRODUCT FOCUS PECAM1 Platelet endothelial cell adhesion of blood vessels – making up a large portion molecule-1 (PECAM1), also known as cluster of its intracellular junctions. PECAM-1 is also CD Number of differentiation 31 (CD31), is a member of present on the surface of hematopoietic the immunoglobulin gene superfamily of cell cells and immune cells including platelets, CD31 adhesion molecules. It is highly expressed monocytes, neutrophils, natural killer cells, on the surface of the endothelium – the thin megakaryocytes and some types of T-cell. Catalog Number layer of endothelial cells lining the interior 11256-1-AP Type Rabbit Polyclonal Applications ELISA, FC, IF, IHC, IP, WB 16 Publications Immunohistochemical of paraffin-embedded Figure 1: Immunofluorescence staining human hepatocirrhosis using PECAM1, CD31 of PECAM1 (11256-1-AP), Alexa 488 goat antibody (11265-1-AP) at a dilution of 1:50 anti-rabbit (green), and smooth muscle KD/KO Validated (40x objective). alpha-actin (red), courtesy of Nicola Smart. PECAM1: Customer Testimonial Nicola Smart, a cardiovascular researcher “As you can see [the immunostaining] is and a group leader at the University of extremely clean and specific [and] displays Oxford, has said of the PECAM1 antibody strong intercellular junction expression, (11265-1-AP) that it “worked beautifully as expected for a cell adhesion molecule.” on every occasion I’ve tried it.” Proteintech thanks Dr.
    [Show full text]
  • The Enzymatic Activities of CD38 Enhance CLL Growth and Trafficking
    Leukemia (2015) 29, 356–368 © 2015 Macmillan Publishers Limited All rights reserved 0887-6924/15 www.nature.com/leu ORIGINAL ARTICLE The enzymatic activities of CD38 enhance CLL growth and trafficking: implications for therapeutic targeting T Vaisitti1,2, V Audrito1,2, S Serra1,2, R Buonincontri1,2, G Sociali3, E Mannino3, A Pagnani2, A Zucchetto4, E Tissino4, C Vitale5, M Coscia5, C Usai6, C Pepper7, V Gattei4, S Bruzzone3 and S Deaglio1,2 The ecto-enzyme CD38 is gaining momentum as a novel therapeutic target for patients with hematological malignancies, with several anti-CD38 monoclonal antibodies in clinical trials with promising results. In chronic lymphocytic leukemia (CLL) CD38 is a marker of unfavorable prognosis and a central factor in the pathogenetic network underlying the disease: activation of CD38 regulates genetic pathways involved in proliferation and movement. Here we show that CD38 is enzymatically active in primary CLL cells and that its forced expression increases disease aggressiveness in a xenograft model. The effect is completely lost when using an enzyme-deficient version of CD38 with a single amino-acid mutation. Through the enzymatic conversion of NAD into ADPR (ADP-ribose) and cADPR (cyclic ADP-ribose), CD38 increases cytoplasmic Ca2+ concentrations, positively influencing proliferation and signaling mediated via chemokine receptors or integrins. Consistently, inhibition of the enzymatic activities of CD38 using the flavonoid kuromanin blocks CLL chemotaxis, adhesion and in vivo homing. In a short-term xenograft model using primary cells, kuromanin treatment traps CLL cells in the blood, thereby increasing responses to chemotherapy. These results suggest that monoclonal antibodies that block the enzymatic activities of CD38 or enzyme inhibitors may prove therapeutically useful.
    [Show full text]
  • Differential Integrin Adhesome Expression Defines Human Natural
    bioRxiv preprint doi: https://doi.org/10.1101/2020.12.01.404806; this version posted December 1, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC 4.0 International license. Differential integrin adhesome expression defines human natural killer cell residency and developmental stage Everardo Hegewisch Solloa1, Seungmae Seo1, Bethany L. Mundy-Bosse2, Anjali Mishra3,a, Erik Waldman4,b, Sarah Maurrasse4,b, Eli Grunstein4, Thomas J. Connors5, Aharon G. Freud2,6, and Emily M. Mace1 1Department of Pediatrics, Columbia University College of Physicians and Surgeons, New York NY 10032 2Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA; Comprehensive Cancer Center and The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH 43210 33Division of Dermatology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA; Comprehensive Cancer Center and The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH 43210 4Department of Otolaryngology - Head and Neck Surgery, Columbia University Medical Center, New York, New York 10032 5Department of Pediatrics, Division of Pediatric Critical Care and Hospital Medicine, Columbia University Irving Medical Center, New York, NY 10024 6Department of Pathology, The Ohio State University, Columbus,
    [Show full text]
  • (P -Value<0.05, Fold Change≥1.4), 4 Vs. 0 Gy Irradiation
    Table S1: Significant differentially expressed genes (P -Value<0.05, Fold Change≥1.4), 4 vs. 0 Gy irradiation Genbank Fold Change P -Value Gene Symbol Description Accession Q9F8M7_CARHY (Q9F8M7) DTDP-glucose 4,6-dehydratase (Fragment), partial (9%) 6.70 0.017399678 THC2699065 [THC2719287] 5.53 0.003379195 BC013657 BC013657 Homo sapiens cDNA clone IMAGE:4152983, partial cds. [BC013657] 5.10 0.024641735 THC2750781 Ciliary dynein heavy chain 5 (Axonemal beta dynein heavy chain 5) (HL1). 4.07 0.04353262 DNAH5 [Source:Uniprot/SWISSPROT;Acc:Q8TE73] [ENST00000382416] 3.81 0.002855909 NM_145263 SPATA18 Homo sapiens spermatogenesis associated 18 homolog (rat) (SPATA18), mRNA [NM_145263] AA418814 zw01a02.s1 Soares_NhHMPu_S1 Homo sapiens cDNA clone IMAGE:767978 3', 3.69 0.03203913 AA418814 AA418814 mRNA sequence [AA418814] AL356953 leucine-rich repeat-containing G protein-coupled receptor 6 {Homo sapiens} (exp=0; 3.63 0.0277936 THC2705989 wgp=1; cg=0), partial (4%) [THC2752981] AA484677 ne64a07.s1 NCI_CGAP_Alv1 Homo sapiens cDNA clone IMAGE:909012, mRNA 3.63 0.027098073 AA484677 AA484677 sequence [AA484677] oe06h09.s1 NCI_CGAP_Ov2 Homo sapiens cDNA clone IMAGE:1385153, mRNA sequence 3.48 0.04468495 AA837799 AA837799 [AA837799] Homo sapiens hypothetical protein LOC340109, mRNA (cDNA clone IMAGE:5578073), partial 3.27 0.031178378 BC039509 LOC643401 cds. [BC039509] Homo sapiens Fas (TNF receptor superfamily, member 6) (FAS), transcript variant 1, mRNA 3.24 0.022156298 NM_000043 FAS [NM_000043] 3.20 0.021043295 A_32_P125056 BF803942 CM2-CI0135-021100-477-g08 CI0135 Homo sapiens cDNA, mRNA sequence 3.04 0.043389246 BF803942 BF803942 [BF803942] 3.03 0.002430239 NM_015920 RPS27L Homo sapiens ribosomal protein S27-like (RPS27L), mRNA [NM_015920] Homo sapiens tumor necrosis factor receptor superfamily, member 10c, decoy without an 2.98 0.021202829 NM_003841 TNFRSF10C intracellular domain (TNFRSF10C), mRNA [NM_003841] 2.97 0.03243901 AB002384 C6orf32 Homo sapiens mRNA for KIAA0386 gene, partial cds.
    [Show full text]
  • Monoclonal Antibodies in Myeloma
    Monoclonal Antibodies in Myeloma Pia Sondergeld, PhD, Niels W. C. J. van de Donk, MD, PhD, Paul G. Richardson, MD, and Torben Plesner, MD Dr Sondergeld is a medical student at the Abstract: The development of monoclonal antibodies (mAbs) for University of Giessen in Giessen, Germany. the treatment of disease goes back to the vision of Paul Ehrlich in Dr van de Donk is a hematologist in the the late 19th century; however, the first successful treatment with department of hematology at the VU a mAb was not until 1982, in a lymphoma patient. In multiple University Medical Center in Amsterdam, The Netherlands. Dr Richardson is the R.J. myeloma, mAbs are a very recent and exciting addition to the Corman Professor of Medicine at Harvard therapeutic armamentarium. The incorporation of mAbs into Medical School, and clinical program current treatment strategies is hoped to enable more effective and leader and director of clinical research targeted treatment, resulting in improved outcomes for patients. at the Jerome Lipper Myeloma Center, A number of targets have been identified, including molecules division of hematologic malignancy, depart- on the surface of the myeloma cell and components of the bone ment of medical oncology, Dana-Farber Cancer Institute in Boston, MA. Dr Plesner marrow microenvironment. Our review focuses on a small number is a professor of hematology at the Univer- of promising mAbs directed against molecules on the surface of sity of Southern Denmark and a consultant myeloma cells, including CS1 (elotuzumab), CD38 (daratumumab, in the department of hematology at Vejle SAR650984, MOR03087), CD56 (lorvotuzumab mertansine), and Hospital in Vejle, Denmark.
    [Show full text]
  • Identification of Key Pathways and Genes in Dementia Via Integrated Bioinformatics Analysis
    bioRxiv preprint doi: https://doi.org/10.1101/2021.04.18.440371; this version posted July 19, 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. Identification of Key Pathways and Genes in Dementia via Integrated Bioinformatics Analysis Basavaraj Vastrad1, Chanabasayya Vastrad*2 1. Department of Biochemistry, Basaveshwar College of Pharmacy, Gadag, Karnataka 582103, India. 2. Biostatistics and Bioinformatics, Chanabasava Nilaya, Bharthinagar, Dharwad 580001, Karnataka, India. * Chanabasayya Vastrad [email protected] Ph: +919480073398 Chanabasava Nilaya, Bharthinagar, Dharwad 580001 , Karanataka, India bioRxiv preprint doi: https://doi.org/10.1101/2021.04.18.440371; this version posted July 19, 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. Abstract To provide a better understanding of dementia at the molecular level, this study aimed to identify the genes and key pathways associated with dementia by using integrated bioinformatics analysis. Based on the expression profiling by high throughput sequencing dataset GSE153960 derived from the Gene Expression Omnibus (GEO), the differentially expressed genes (DEGs) between patients with dementia and healthy controls were identified. With DEGs, we performed a series of functional enrichment analyses. Then, a protein–protein interaction (PPI) network, modules, miRNA-hub gene regulatory network and TF-hub gene regulatory network was constructed, analyzed and visualized, with which the hub genes miRNAs and TFs nodes were screened out. Finally, validation of hub genes was performed by using receiver operating characteristic curve (ROC) analysis.
    [Show full text]
  • B3GAT1 Antibody Cat
    B3GAT1 Antibody Cat. No.: 64-189 B3GAT1 Antibody Flow cytometric analysis of K562 cells (right histogram) compared to a negative control cell (left histogram).FITC-conjugated goat-anti- rabbit secondary antibodies were used for the analysis. Specifications HOST SPECIES: Rabbit SPECIES REACTIVITY: Human This B3GAT1 antibody is generated from rabbits immunized with a KLH conjugated IMMUNOGEN: synthetic peptide between 21-48 amino acids from the N-terminal region of human B3GAT1. TESTED APPLICATIONS: Flow, WB For WB starting dilution is: 1:1000 APPLICATIONS: For FACS starting dilution is: 1:10~50 PREDICTED MOLECULAR 38 kDa WEIGHT: September 26, 2021 1 https://www.prosci-inc.com/b3gat1-antibody-64-189.html Properties This antibody is purified through a protein A column, followed by peptide affinity PURIFICATION: purification. CLONALITY: Polyclonal ISOTYPE: Rabbit Ig CONJUGATE: Unconjugated PHYSICAL STATE: Liquid BUFFER: Supplied in PBS with 0.09% (W/V) sodium azide. CONCENTRATION: batch dependent Store at 4˚C for three months and -20˚C, stable for up to one year. As with all antibodies STORAGE CONDITIONS: care should be taken to avoid repeated freeze thaw cycles. Antibodies should not be exposed to prolonged high temperatures. Additional Info OFFICIAL SYMBOL: B3GAT1 Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 1, Beta-1,3- ALTERNATE NAMES: glucuronyltransferase 1, Glucuronosyltransferase P, GlcAT-P, UDP-GlcUA:glycoprotein beta-1,3-glucuronyltransferase, GlcUAT-P, B3GAT1, GLCATP ACCESSION NO.: Q9P2W7 PROTEIN GI NO.: 205830910 GENE ID: 27087 USER NOTE: Optimal dilutions for each application to be determined by the researcher. Background and References The protein encoded by this gene is a member of the glucuronyltransferase gene family.
    [Show full text]