liu.seSearch for publications in DiVA
Change search
Refine search result
1 - 15 of 15
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1.
    Cossarizza, Andrea
    et al.
    University of Modena, Italy; Reggio Emilia School Med, Italy.
    Chang, Hyun-Dong
    Institute Leibniz Assoc, Germany.
    Radbruch, Andreas
    Institute Leibniz Assoc, Germany.
    Andrae, Immanuel
    Technical University of Munich, Germany.
    Annunziato, Francesco
    University of Florence, Italy.
    Bacher, Petra
    Charite University of Medical Berlin, Germany.
    Barnaba, Vincenzo
    Sapienza University of Roma, Italy; Fdn Cenci Bolognetti, Italy.
    Battistini, Luca
    Santa Lucia Fdn, Italy.
    Bauer, Wolfgang M.
    Medical University of Vienna, Austria.
    Baumgart, Sabine
    Institute Leibniz Assoc, Germany.
    Becher, Burkhard
    University of Zurich, Switzerland.
    Beisker, Wolfgang
    German Research Centre Environm Heatlh, Germany.
    Berek, Claudia
    Institute Leibniz Assoc, Germany.
    Blanco, Alfonso
    University of Coll Dublin, Ireland.
    Borsellino, Giovanna
    Santa Lucia Fdn, Italy.
    Boulais, Philip E.
    Albert Einstein Coll Med, NY 10467 USA; Ruth L and David S Gottesman Institute Stem Cell and Regen, NY USA.
    Brinkman, Ryan R.
    BC Cancer Agency, Canada; University of British Columbia, Canada.
    Buescher, Martin
    Miltenyi Biotec GmbH, Germany.
    Busch, Dirk H.
    Technical University of Munich, Germany; National Centre Infect Research, Germany; Technical University of Munich, Germany.
    Bushnell, Timothy P.
    University of Rochester, NY 14642 USA; University of Rochester, NY 14642 USA.
    Cao, Xuetao
    Zhejiang University, Peoples R China; Second Mil Medical University, Peoples R China; Second Mil Medical University, Peoples R China; Chinese Academic Medical Science, Peoples R China; Chinese Academic Medical Science, Peoples R China.
    Cavani, Andrea
    NIHMP, Italy.
    Chattopadhyay, Pratip K.
    Vaccine Research Centre, MD USA.
    Cheng, Qingyu
    Charite University of Medical Berlin, Germany.
    Chow, Sue
    Princess Margaret Hospital, Canada.
    Clerici, Mario
    University of Milan, Italy; Fdn Don C Gnocchi, Italy.
    Cooke, Anne
    University of Cambridge, England.
    Cosma, Antonio
    University of Paris Sud, France.
    Cosmi, Lorenzo
    University of Firenze, Italy.
    Cumano, Ana
    Pasteur Institute, France.
    Duc Dang, Van
    Institute Leibniz Assoc, Germany.
    Davies, Derek
    Francis Crick Institute, England.
    De Biasi, Sara
    University of Modena and Reggio Emilia, Italy.
    Del Zotto, Genny
    Ist Giannina Gaslini, Italy.
    Della Bella, Silvia
    University of Milan, Italy; Lab Clin and Expt Immunol, Italy.
    Dellabona, Paolo
    Ist Science San Raffaele, Italy.
    Deniz, Gunnur
    Istanbul University, Turkey.
    Dessing, Mark
    Sony Europe Ltd, England.
    Diefenbach, Andreas
    Charite University of Medical Berlin, Germany.
    Di Santo, James
    Institute Pasteur, France.
    Dieli, Francesco
    University of Palermo, Italy.
    Dolf, Andreas
    University of Bonn, Germany.
    Donnenberg, Vera S.
    University of Pittsburgh, PA USA.
    Doerner, Thomas
    Charite University of Medical Berlin, Germany.
    Ehrhardt, Gotz R. A.
    University of Toronto, Canada.
    Endl, Elmar
    University of Bonn, Germany.
    Engel, Pablo
    University of Barcelona, Spain.
    Engelhardt, Britta
    University of Bern, Switzerland.
    Esser, Charlotte
    Leibniz Research Institute Environm Med, Germany.
    Everts, Bart
    Leiden University, Netherlands.
    Falk, Christine S.
    MHH Hannover Medical Sch, Germany; TTU IICH, Germany.
    Fehniger, Todd A.
    Washington University, MO USA.
    Filby, Andrew
    Newcastle University, England.
    Fillatreau, Simon
    INSERM, France; University of Paris 05, France; Hop Necker Enfants Malad, France.
    Follo, Marie
    University of Freiburg, Germany.
    Foerster, Irmgard
    University of Bonn, Germany.
    Foster, John
    Owl Biomed Inc, CA USA.
    Foulds, Gemma A.
    Nottingham Trent University, England.
    Frenette, Paul S.
    Albert Einstein Coll Med, NY 10467 USA.
    Galbraith, David
    University of Arizona, AZ USA.
    Garbi, Natalio
    University of Bonn, Germany; Arizona Cancer Centre, AZ USA; Institute Expt Immunol, Germany.
    Dolores Garcia-Godoy, Maria
    Josep Carreras Leukemia Research Institute, Spain.
    Geginat, Jens
    Ist Nazl Genet Molecolare Romeo Enrica Invernizzi, Italy.
    Ghoreschi, Kamran
    Eberhard Karls University of Tubingen, Germany.
    Gibellini, Lara
    University of Modena and Reggio Emilia, Italy.
    Goettlinger, Christoph
    University of Cologne, Germany.
    Goodyear, Carl S.
    University of Glasgow, Scotland.
    Gori, Andrea
    University of Milano Bicocca, Italy.
    Grogan, Jane
    Genentech Inc, CA USA.
    Gross, Mor
    Weizmann Institute Science, Israel.
    Gruetzkau, Andreas
    Institute Leibniz Assoc, Germany.
    Grummitt, Daryl
    Owl Biomed Inc, CA USA.
    Hahn, Jonas
    University of Klinikum Erlangen, Germany.
    Hammer, Quirin
    Institute Leibniz Assoc, Germany.
    Hauser, Anja E.
    Institute Leibniz Assoc, Germany; Charite University of Medical Berlin, Germany.
    Haviland, David L.
    Houston Methodist Hospital, TX USA.
    Hedley, David
    Princess Margaret Hospital, Canada.
    Herrera, Guadalupe
    University of Valencia, Spain; University of Valencia, Spain.
    Herrmann, Martin
    University of Klinikum Erlangen, Germany.
    Hiepe, Falk
    Charite University of Medical Berlin, Germany.
    Holland, Tristan
    Arizona Cancer Centre, AZ USA; Institute Expt Immunol, Germany.
    Hombrink, Pleun
    Sanquin Research and Landsteiner Lab, Netherlands.
    Houston, Jessica P.
    New Mexico State University, NM 88003 USA.
    Hoyer, Bimba F.
    Charite University of Medical Berlin, Germany.
    Huang, Bo
    Huazhong University of Science and Technology, Peoples R China; Chinese Academic Medical Science, Peoples R China; Chinese Academic Medical Science, Peoples R China; Peking Union Medical Coll, Peoples R China; Chinese Academic Medical Science, Peoples R China.
    Hunter, Christopher A.
    University of Penn, PA 19104 USA.
    Iannone, Anna
    University of Modena and Reggio Emilia, Italy.
    Jaeck, Hans-Martin
    University Hospital Erlangen, Germany.
    Javega, Beatriz
    University of Valencia, Spain.
    Jonjic, Stipan
    University of Rijeka, Croatia; University of Rijeka, Croatia.
    Juelke, Kerstin
    Institute Leibniz Assoc, Germany.
    Jung, Steffen
    Weizmann Institute Science, Israel.
    Kaiser, Toralf
    Institute Leibniz Assoc, Germany.
    Kalina, Tomas
    Charles University of Prague, Czech Republic; University Hospital Motol, Czech Republic.
    Keller, Baerbel
    University of Freiburg, Germany.
    Khan, Srijit
    University of Toronto, Canada.
    Kienhoefer, Deborah
    University of Klinikum Erlangen, Germany.
    Kroneis, Thomas
    Medical University of Graz, Austria.
    Kunkel, Desiree
    Charite University of Medical Berlin, Germany.
    Kurts, Christian
    University of Bonn, Germany.
    Kvistborg, Pia
    Netherlands Cancer Institute, Netherlands.
    Lannigan, Joanne
    University of Virginia, VA 22908 USA.
    Lantz, Olivier
    Institute Curie, France; Institute Curie, France; Institute Curie, France.
    Larbi, Anis
    Biol Aging Program, Singapore; ASTAR, Singapore; University of Sherbrooke, Canada; ElManar University, Tunisia.
    LeibundGut-Landmann, Salome
    University of Zurich, Switzerland.
    Leipold, Michael D.
    Stanford University, CA USA.
    Levings, Megan K.
    University of British Columbia, Canada; British Columbia Childrens Hospital, Canada.
    Litwin, Virginia
    Covance, IN USA.
    Liu, Yanling
    University of Toronto, Canada.
    Lohoff, Michael
    University of Marburg, Germany; University of Marburg, Germany.
    Lombardi, Giovanna
    Guys Hospital, England.
    Lopez, Lilly
    Beckman Coulter Inc, FL USA.
    Lovett-Racke, Amy
    Ohio State University, OH 43210 USA.
    Lubberts, Erik
    University of Medical Centre, Netherlands.
    Ludewig, Burkhard
    Kantonsspital St Gallen, Switzerland.
    Lugli, Enrico
    Humanitas Clin and Research Centre, Italy; Humanitas Clin and Research Centre, Italy.
    Maecker, Holden T.
    Stanford University, CA USA.
    Martrus, Gloria
    Leibniz Institute Expt Virol, Germany.
    Matarese, Giuseppe
    University of Napoli Federico II, Italy; IEOS, Italy.
    Maueroeder, Christian
    University of Klinikum Erlangen, Germany.
    McGrath, Mairi
    Institute Leibniz Assoc, Germany.
    McInnes, Iain
    University of Glasgow, Scotland.
    Mei, Henrik E.
    Institute Leibniz Assoc, Germany.
    Melchers, Fritz
    Max Planck Institute Infect Biol, Germany.
    Melzer, Susanne
    University of Leipzig, Germany.
    Mielenz, Dirk
    University of Erlangen Nurnberg, Germany.
    Mills, Kingston
    University of Dublin, Ireland.
    Mjösberg, Jenny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Institute Stockholm, Sweden.
    Moore, Jonni
    University of Penn, PA USA.
    Moran, Barry
    University of Dublin, Ireland.
    Moretta, Alessandro
    University of Genoa, Italy; Centre Eccellenza Ric Biomed CEBR, Italy.
    Moretta, Lorenzo
    Bambino Gesu Pediat Hospital, Italy.
    Mosmann, Tim R.
    University of Rochester, NY 14642 USA.
    Mueller, Susann
    UFZ Helmholtz Centre Environm Research, Germany.
    Muller, Werner
    University of Manchester, England.
    Munz, Christian
    University of Zurich, Switzerland.
    Multhoff, Gabriele
    Technical University of Munchen TUM, Germany; Helmholtz Zentrum Munchen, Germany.
    Enrique Munoz, Luis
    University of Klinikum Erlangen, Germany.
    Murphy, Kenneth M.
    Washington University of St Louis, MO USA; Washington University of St Louis, MO USA.
    Nakayama, Toshinori
    Chiba University, Japan.
    Nasi, Milena
    University of Modena and Reggio Emilia, Italy.
    Neudoerfl, Christine
    MHH Hannover Medical Sch, Germany.
    Nolan, John
    Scintillon Institute, CA USA.
    Nourshargh, Sussan
    William Harvey Research Institute, England; Queen Mary University of London, England.
    OConnor, Jose-Enrique
    University of Valencia, Spain.
    Ouyang, Wenjun
    Amgen Inc, CA USA.
    Oxenius, Annette
    Swiss Federal Institute Technology, Switzerland.
    Palankar, Raghav
    University of Medical Greifswald, Germany.
    Panse, Isabel
    University of Oxford, England.
    Peterson, Part
    University of Tartu, Estonia.
    Peth, Christian
    Miltenyi Biotec GmbH, Germany.
    Petriz, Jordi
    Josep Carreras Leukemia Research Institute, Spain.
    Philips, Daisy
    Netherlands Cancer Institute, Netherlands.
    Pickl, Winfried
    Medical University of Vienna, Austria.
    Piconese, Silvia
    Sapienza University of Roma, Italy; Fdn Cenci Bolognetti, Italy.
    Pinti, Marcello
    University of Modena and Reggio Emilia, Italy.
    Graham Pockley, A.
    Nottingham Trent University, England; Chromocyte Ltd, England.
    Justyna Podolska, Malgorzata
    University of Klinikum Erlangen, Germany.
    Pucillo, Carlo
    University of Udine, Italy.
    Quataert, Sally A.
    University of Rochester, NY 14642 USA.
    Radstake, Timothy R. D. J.
    University of Medical Centre Utrecht, Netherlands; University of Medical Centre Utrecht, Netherlands.
    Rajwa, Bartek
    Purdue University, IN 47907 USA.
    Rebhahn, Jonathan A.
    University of Rochester, NY 14642 USA.
    Recktenwald, Diether
    Desatoya LLC, NV USA.
    Remmerswaal, Ester B. M.
    Academic Medical Centre, Netherlands; Academic Medical Centre, Netherlands.
    Rezvani, Katy
    University of Texas MD Anderson Cancer Centre, TX 77030 USA.
    Rico, Laura G.
    Josep Carreras Leukemia Research Institute, Spain.
    Paul Robinson, J.
    Purdue University, IN 47907 USA.
    Romagnani, Chiara
    Institute Leibniz Assoc, Germany.
    Rubartelli, Anna
    IRCCS, Italy.
    Ruland, Juergen
    Technical University of Munich, Germany; German Cancer Research Centre, Germany.
    Sakaguchi, Shimon
    Osaka University, Japan; Kyoto University, Japan.
    Sala-de-Oyanguren, Francisco
    University of Valencia, Spain.
    Samstag, Yvonne
    Ruprecht Karls University of Heidelberg, Germany.
    Sanderson, Sharon
    University of Oxford, England.
    Sawitzki, Birgit
    Free University of Berlin, Germany; Institute Medical Immunol, Germany.
    Scheffold, Alexander
    Institute Leibniz Assoc, Germany; Charite University of Medical Berlin, Germany.
    Schiemann, Matthias
    Technical University of Munich, Germany.
    Schildberg, Frank
    Harvard Medical Sch, MA USA.
    Schimisky, Esther
    Miltenyi Biotec GmbH, Germany.
    Schmid, Stephan A.
    University of Klinikum Regensburg, Germany.
    Schmitt, Steffen
    German Cancer Research Centre, Germany.
    Schober, Kilian
    Technical University of Munich, Germany.
    Schueler, Thomas
    Otto Von Guericke University, Germany.
    Ronald Schulz, Axel
    Institute Leibniz Assoc, Germany.
    Schumacher, Ton
    Netherlands Cancer Institute, Netherlands.
    Scotta, Cristiano
    Guys Hospital, England.
    Vincent Shankey, T.
    AsedaSciences, IN USA.
    Shemer, Anat
    Weizmann Institute Science, Israel.
    Simon, Anna-Katharina
    University of Oxford, England.
    Spidlen, Josef
    BC Cancer Agency, Canada.
    Stall, Alan M.
    BD Life Science, CA USA.
    Stark, Regina
    Sanquin Research and Landsteiner Lab, Netherlands.
    Stehle, Christina
    Institute Leibniz Assoc, Germany.
    Stein, Merle
    University of Erlangen Nurnberg, Germany.
    Steinmetz, Tobit
    University of Erlangen Nurnberg, Germany.
    Stockinger, Hannes
    Medical University of Vienna, Austria.
    Takahama, Yousuke
    University of Tokushima, Japan.
    Tarnok, Attila
    Fraunhofer Institute Cell Therapy and Immunol IZI, Germany; IMISE, Germany.
    Tian, ZhiGang
    University of Science and Technology China, Peoples R China; University of Science and Technology China, Peoples R China; Zhejiang University, Peoples R China.
    Tornack, Julia
    Max Planck Institute Infect Biol, Germany.
    Traggiai, Elisabetta
    NIBR, Switzerland.
    Trotter, Joe
    BD Life Science, CA USA.
    Ulrich, Henning
    University of Sao Paulo, Brazil.
    van der Braber, Marlous
    Netherlands Cancer Institute, Netherlands.
    van Lier, Rene A. W.
    Sanquin Research and Landsteiner Lab, Netherlands.
    Veldhoen, Marc
    Institute Molecular Med, Portugal.
    Vento-Asturias, Salvador
    Arizona Cancer Centre, AZ USA.
    Vieira, Paulo
    Institute Pasteur, France.
    Voehringer, David
    University Hospital Erlangen, Germany.
    Volk, Hans-Dieter
    Labor Berlin, Germany.
    von Volkmann, Konrad
    APE Appl Phys and Elect, Germany.
    Waisman, Ari
    Johannes Gutenberg University of Mainz, Germany.
    Walker, Rachael
    Babraham Institute, England.
    Ward, Michael D.
    Thermo Fisher Science, OR USA.
    Warnatz, Klaus
    University of Freiburg, Germany.
    Warth, Sarah
    Charite University of Medical Berlin, Germany.
    Watson, James V.
    Medinfomat Ltd, England.
    Watzl, Carsten
    TU Dortmund, Germany.
    Wegener, Leonie
    Miltenyi Biotec GmbH, Germany.
    Wiedemann, Annika
    Charite University of Medical Berlin, Germany.
    Wienands, Juergen
    University of Medical Gottingen, Germany.
    Wing, James
    Osaka University, Japan; Kyoto University, Japan.
    Wurst, Peter
    University of Bonn, Germany.
    Yu, Liping
    BD Bioscience, CA USA.
    Yue, Alice
    Simon Fraser University, Canada.
    Zhang, Qianjun
    Emerald Biotech Co Ltd, Peoples R China.
    Zhao, Yi
    Sichuan University, Peoples R China.
    Ziegler, Susanne
    Leibniz Institute Expt Virol, Germany.
    Zimmermann, Jakob
    University of Bern, Switzerland.
    Guidelines for the use of flow cytometry and cell sorting in immunological studies2017In: European Journal of Immunology, ISSN 0014-2980, E-ISSN 1521-4141, Vol. 47, no 10, p. 1584-1797Article in journal (Refereed)
    Abstract [en]

    n/a

  • 2.
    Edström, Måns
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Dahle, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Mellergård, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Neurology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Mjösberg, Jenny
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Press, Rayomand
    Karolinska Hospital.
    Vrethem, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Neurology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Th1/Th2/Th17 and Treg related transcription factors and cytokines in multiple sclerosis2008In: JOURNAL OF NEUROIMMUNOLOGY, 2008, Vol. 203, no 2, p. 131-132Conference paper (Refereed)
  • 3.
    Edström, Måns
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Mellergård, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Mjösberg, Jenny
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Vrethem, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Press, R
    Huddinge University Hospital.
    Dahle, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Transcriptional characteristics of CD4+ T cells in multiple sclerosis: relative lack of suppressive populations in blood2011In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 17, no 1, p. 57-66Article in journal (Refereed)
    Abstract [en]

    Background:Multiple sclerosis (MS) is hypothetically caused by autoreactive Th1 and Th17 cells, whereas Th2 and regulatory T cells may confer protection. The development of Th subpopulations is dependant on the expression of lineage-specific transcription factors.

    Objective:The aim of this study was to assess the balance of CD4+T cell populations in relapsing-remitting MS.

    Methods:Blood mRNA expression of TBX21, GATA3, RORC, FOXP3 and EBI3 was assessed in 33 patients with relapsing-remitting MS and 20 healthy controls. In addition, flow cytometry was performed to assess T lymphocyte numbers.

    Results:In relapsing-remitting MS, diminished expression of FOXP3 (Treg) was found (p < 0.05), despite normal numbers of CD4+CD25hiTreg. Immunoregulatory EBI3 and Th2-associated GATA3 ([a-z]+) was also decreased in MS (p < 0.005 and p < 0.05, respectively). Expression of TBX21 (Th1) and RORC (Th17) did not differ between patients and controls. Similar changes were observed when analysing beta-interferon treated (n = 12) or untreated (n = 21) patients. Analysis of transcription factor ratios, comparing TBX21/GATA3 and RORC/FOXP3, revealed an increase in the RORC/FOXP3 ratio in patients with relapsing-remitting MS (p < 0.005).

    Conclusion:Our findings indicate systemic defects at the mRNA level, involving downregulation of beneficial CD4+phenotypes. This might play a role in disease development by permitting activation of harmful T cell populations.

  • 4.
    Ernerudh, Jan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Berg, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Mjösberg, Jenny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology.
    Regulatory T Helper Cells in Pregnancy and their Roles in Systemic versus Local Immune Tolerance2011In: AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, ISSN 1046-7408, Vol. 66, p. 31-43Article, review/survey (Refereed)
    Abstract [en]

    Problem During pregnancy, the maternal immune system needs to adapt in order not to reject the semi-allogenic fetus. Method In this review, we describe and discuss the role of regulatory T (Treg) cells in fetal tolerance. Results Treg cells constitute a T helper lineage that is derived from thymus (natural Treg cells) or is induced in the periphery (induced Treg cells). Treg cells are enriched at the fetal-maternal interface, showing a suppressive phenotype. In contrast, Treg cells are not increased in the circulation of pregnant women, and the suppressive capacity is similar to that in nonpregnant women. However, aberrations in Treg frequencies and functions, both systemically and in the uterus, may be involved in the complications of pregnancy. Conclusion Treg cells seem to have distinguished roles locally versus systemically, based on their distribution and phenotype.

  • 5.
    Ernerudh, Jan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Forsberg, Anna
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Straka, E
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Johansson, Ewa
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Bhai Mehta, Ratnesh
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Svensson, J
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Matthiesen, Leif
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Boij, R
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Berg, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Mjösberg, Jenny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    T helper cells and T helper cell plasticity in pregnancy in JOURNAL OF REPRODUCTIVE IMMUNOLOGY, vol 90, issue 2, pp 131-1312011In: JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Elsevier , 2011, Vol. 90, no 2, p. 131-131Conference paper (Refereed)
    Abstract [en]

    n/a

  • 6.
    Gustafsson (Lidström), Charlotte
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences.
    Mjösberg, Jenny
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences.
    Matussek, Andreas
    Department of Clinical Microbiology, County Hospital Ryhov, Jönköping, Sweden.
    Geffers, Robert
    Mucosal Immunity, Helmholtz Centre for Infection Research (HCI), Braunschweig, Germany.
    Matthiesen, Leif
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology . Linköping University, Faculty of Health Sciences.
    Berg, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology . Linköping University, Faculty of Health Sciences.
    Sharma, Surendra
    Department of Pediatrics, Brown University and Women and Infants' Hospital of Rhode Island, Providence, Rhode Island, United States of America.
    Buer, Jan
    Institute of Medical Microbiology, University Hospital Essen, Essen, Germany.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences.
    Gene expression profiling of human decidual macrophages: Evidence for immunosuppressive phenotype2008In: PLoS ONE, ISSN 1932-6203, Vol. 3, no 4, p. e2078-Article in journal (Refereed)
    Abstract [en]

    Background: Although uterine macrophages are thought to play an important regulatory role at the maternal-fetal interface, their global gene expression profile is not known.

    Methodology/Principal Findings: Using micro-array comprising approximately 14,000 genes, the gene expression pattern of human first trimester decidual CD14+ monocytes/macrophages was characterized and compared with the expression profile of the corresponding cells in blood. Some of the key findings were confirmed by real time PCR or by secreted protein. A unique gene expression pattern intrinsic of first trimester decidual CD14+ cells was demonstrated. A large number of regulated genes were functionally related to immunomodulation and tissue remodelling, corroborating polarization patterns of differentiated macrophages mainly of the alternatively activated M2 phenotype. These include known M2 markers such as CCL-18, CD209, insulin-like growth factor (IGF)-1, mannose receptor c type (MRC)-1 and fibronectin-1. Further, the selective up-regulation of triggering receptor expressed on myeloid cells (TREM)-2, alpha-2-macroglobulin (A2M) and prostaglandin D2 synthase (PGDS) provides new insights into the regulatory function of decidual macrophages in pregnancy that may have implications in pregnancy complications.

    Conclusions/Significance: The molecular characterization of decidual macrophages presents a unique transcriptional profile replete with important components for fetal immunoprotection and provides several clues for further studies of these cells.

  • 7.
    Mjösberg, Jenny
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Regulatory T cells in human pregnancy2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    During pregnancy, fetal tolerance has to be achieved without compromising the immune integrity of the mother. CD4+CD25highFoxp3+ regulatory cells (Tregs) have received vast attention as key players in immune regulation. However, the identification of human Tregs is complicated by their similarity to activated nonsuppressive T cells. The general aim of this thesis was to determine the antigen specificity, frequency, phenotype and function of Tregs in first to second trimester healthy and severe early-onset preeclamptic human pregnancy. Regarding antigen specificity, we observed that in healthy pregnant women, Tregs suppressed both TH1 and TH2 reactions when stimulated with paternal alloantigens but only TH1, not TH2 reactions when stimulated with unrelated alloantigens. Hence, circulating paternal-specific Tregs seem to be present during pregnancy. Further, by strictly defining typical Tregs (CD4dimCD25high) using flow cytometry, we could show that as a whole, the Treg population was reduced already during first trimester pregnancy as compared with non-pregnant women. This was in contrast to several previous studies and the discrepancy was most likely due to the presence of activated non-suppressive cells in pregnant women, showing similarities to the suppressive Tregs. Although deserving confirmation in a larger sample, severe early-onset preeclampsia did not seem to be associated with alterations in the circulating Treg population. The circulating Treg population was controlled by hormones which, alike pregnancy, reduced the frequency of Foxp3 expressing cells. Yet, in vitro, pregnancy Tregs were highly suppressive of pro-inflammatory cytokine secretion and showed an enhanced capability of secreting immune modulatory cytokines such as IL-4 and IL-10, as well as IL-17, indicating an increased plasticity of pregnancy Tregs. At the fetalmaternal interface during early pregnancy, Tregs, showing an enhanced suppressive and proliferating phenotype, were enriched as compared with blood. Further, CCR6- TH1 cells, with a presumed moderate TH1 activity were enhanced, whereas pro-inflammatory TH17 and CCR6+ TH1 cells were fewer as compared with blood. This thesis adds to and extends the view of Tregs as key players in immune regulation during pregnancy. In decidua, typical Tregs seem to have an important role in immune suppression whereas systemically, Tregs are under hormonal control and are numerically suppressed during pregnancy. Further, circulating pregnancy Tregs show reduced expression of Foxp3 and an increased degree of cytokine secretion and thereby also possibly plasticity. This would ensure systemic defense against infections with simultaneous tolerance at the fetal-maternal interface during pregnancy.

    List of papers
    1. CD4+ CD25+ regulatory T cells in human pregnancy: Development of a Treg-MLC-ELISPOT suppression assay and indications of paternal specific Tregs
    Open this publication in new window or tab >>CD4+ CD25+ regulatory T cells in human pregnancy: Development of a Treg-MLC-ELISPOT suppression assay and indications of paternal specific Tregs
    2007 (English)In: Immunology, ISSN 0019-2805, E-ISSN 1365-2567, Vol. 120, no 4, p. 456-466Article in journal (Refereed) Published
    Abstract [en]

    The current study was aimed at developing a one-way mixed leucocyte culture-enzyme-linked immunospot (MLC-ELISPOT) assay for the study of CD4 + CD25+ regulatory T (Treg) cells and applying this method in the study of antifetal immune reactions during human pregnancy. Twenty-one pregnant women and the corresponding fathers-to-be, and 10 non-pregnant control women and men, participated in the study. CD4+ CD25+ cells were isolated from peripheral blood mononuclear cells (PBMC) by immunomagnetic selection. Maternal/control PBMC were stimulated with paternal or unrelated PBMC in MLC. Secretion of interleukin-4 (IL-4) and interferon-γ (IFN-γ) from responder cells, with or without the presence of autologous Treg cells, was analysed by ELISPOT. PBMC from pregnant women showed increased secretion of IL-4 compared to controls. In pregnant and non-pregnant controls, Treg cells suppressed IFN-γ reactivity against paternal and unrelated alloantigens. Interestingly, T reg cells suppressed IL-4 secretion against paternal but not unrelated alloantigens during pregnancy. We have successfully developed a model for studying Treg cells in antifetal cytokine reactions during pregnancy. Results indicate that Treg cells contribute to strict regulation of both T helper type 1-like and type 2-like antifetal immune reactions. Interestingly, T helper type 2-like cells specific to unrelated alloantigens are able to escape the suppression of Treg cells, which would allow for IL-4, alongside CD4+ CD25+ Treg cells, to control potentially detrimental IFN-γ reactions during pregnancy. © 2007 Blackwell Publishing Ltd.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-37719 (URN)10.1111/j.1365-2567.2006.02529.x (DOI)37846 (Local ID)37846 (Archive number)37846 (OAI)
    Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13
    2. Systemic reduction of functionally suppressive CD4dimCD25highFoxp3+ Tregs in human second trimester pregnancy is induced by progesterone and 17θ-estradiol
    Open this publication in new window or tab >>Systemic reduction of functionally suppressive CD4dimCD25highFoxp3+ Tregs in human second trimester pregnancy is induced by progesterone and 17θ-estradiol
    Show others...
    2009 (English)In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 183, no 1, p. 759-769Article in journal (Refereed) Published
    Abstract [en]

    CD4+CD25high regulatory T cells (Tregs) are implicated in the maintenance of murine pregnancy. However, reports regarding circulating Treg frequencies in human pregnancy are inconsistent, and the functionality and phenotype of these cells in pregnancy have not been clarified. The aim of this study was to determine the frequency, phenotype, and function of circulating Tregs in the second trimester of human pregnancy and the influence of progesterone and 17β-estradiol on Treg phenotype and frequency. Based on expressions of Foxp3, CD127, and HLA-DR as determined by multicolor flow cytometry, we defined a proper CD4dimCD25high Treg population and showed, in contrast to most previous reports, that this population was reduced in second trimester of pregnancy. Unexpectedly, Foxp3 expression was decreased in the Treg, as well as in the CD4+ population. These changes could be replicated in an in vitro system resembling the pregnancy hormonal milieu, where 17β-estradiol, and in particular progesterone, induced, in line with the pregnancy situation, a reduction of CD4dimCD25highFoxp3+ cells in PBMC from nonpregnant women. By coculturing FACS-sorted Tregs and autologous CD4+CD25 responder cells, we showed that Tregs from pregnant women still displayed the same suppressive capacity as nonpregnant women in terms of suppressing IL-2, TNF-, and IFN- secretion from responder cells while efficiently producing IL-4 and IL-10. Our findings support the view of hormones, particularly progesterone, as critical regulators of Tregs in pregnancy. Furthermore, we suggest that in the light of the results of this study, early data on circulating Treg frequencies in pregnancy need reevaluation.

    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 accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-53104 (URN)10.4049/jimmunol.0803654 (DOI)000275119400082 ()19535629 (PubMedID)
    Available from: 2010-01-26 Created: 2010-01-15 Last updated: 2017-12-12Bibliographically approved
    3. Circulating CD4dimCD25highFOXP3+ regulatory T cells in severe early-onset preeclampsia
    Open this publication in new window or tab >>Circulating CD4dimCD25highFOXP3+ regulatory T cells in severe early-onset preeclampsia
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Preeclampsia is an inflammatory condition suggested to involve regulatory CD4+CD25high T helper cell (Treg) disturbances. However, the importance of Tregs in early-onset preeclampsia, associated with increased disease severity and possibly representing a more distinct placental disease, remains unclear. We recently showed that by defining Tregs as CD4dimCD25high cells, the risk of including activated non-Tregs, being more prominent in the circulation during pregnancy, is avoided. The aim of this study was to determine, using updated Treg markers and flow cytometric gating strategies, the frequency and phenotype of circulating Tregs from women with severe early-onset preeclampsia (n=10) as compared with healthy pregnant (n=20) and nonpregnant (n=20) women. The frequency of CD4dimCD25high cells and the expression of FOXP3 was similar in healthy and preeclamptic pregnancy. However, the occurrence of CTLA-4+ and HLA-DR+ cells in the Treg population from preeclamptic women tended to be higher than in healthy pregnant women, indicating alterations in Treg functionality in preeclampsia. Further, the Treg population from healthy pregnant, but not preeclamptic, women tended to be enriched for CCR4+ and CD45R0+ cells as compared with nonpregnant women. In conclusion, although the findings do not support a role for diminished circulating Treg frequency in severe early-onset preeclampsia, the study suggests functional alterations related to Treg suppression, activation and migration mechanisms in this subgroup of preeclamptic women.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-53617 (URN)
    Available from: 2010-01-26 Created: 2010-01-26 Last updated: 2010-01-26
    4. FOXP3+ regulatory T cells, T helper 1, T helper 2 and T helper 17 cells in human early pregnancy decidua
    Open this publication in new window or tab >>FOXP3+ regulatory T cells, T helper 1, T helper 2 and T helper 17 cells in human early pregnancy decidua
    2010 (English)In: Biology of Reproduction, ISSN 0006-3363, E-ISSN 1529-7268, Vol. 82, no 4, p. 698-705Article in journal (Refereed) Published
    Abstract [en]

    In pregnancy, the decidua is infiltrated by leukocytes promoting fetal development without causing immunological rejection. Murine regulatory T (Treg) cells are known to be important immune regulators at this site. The aim of the study was to characterize the phenotype and origin of Treg cells and determine the quantitative relationship between Treg, T-helper type 1 (TH1), TH2, and TH17 cells in first-trimester human decidua. Blood and decidual CD4+ T cells from 18 healthy first-trimester pregnant women were analyzed for expression of Treg-cell markers (CD25, FOXP3, CD127, CTLA4, and human leukocyte antigen-DR [HLA-DR]), chemokine receptors (CCR4, CCR6, and CXCR3), and the proliferation antigen MKI67 by six-color flow cytometry. Treg cells were significantly enriched in decidua and displayed a more homogenous suppressive phenotype with more frequent expression of FOXP3, HLA-DR, and CTLA4 than in blood. More decidual Treg cells expressed MKI67, possibly explaining their enrichment at the fetal-maternal interface. Using chemokine receptor expression profiles of CCR4, CCR6, and CXCR3 as markers for TH1, TH2, and TH17 cells, we showed that TH17 cells were nearly absent in decidua, whereas TH2-cell frequencies were similar in blood and decidua. CCR6+ TH1 cells, reported to secrete high levels of interferon gamma (IFNG), were fewer, whereas the moderately IFNG-secreting CCR6 TH1 cells were more frequent in decidua compared with blood. Our results point toward local expansion of Treg cells and low occurrence of TH17 cells. Furthermore, local, moderate TH1 activity seems to be a part of normal early pregnancy, consistent with a mild inflammatory environment controlled by Treg cells.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-53616 (URN)10.1095/biolreprod.109.081208 (DOI)000275814400007 ()20018909 (PubMedID)
    Note

    Published online before print December 16, 2009,

    Available from: 2010-01-26 Created: 2010-01-26 Last updated: 2017-12-12
  • 8.
    Mjösberg, Jenny
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology.
    Berg, Göran
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Ernerudh, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Ekerfelt, Christina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology.
    CD4+ CD25+ regulatory T cells in human pregnancy - development of a Treg-MLC elispot assay.2005In: American Society for Reproductive Immunology 2005,2005, 2005, p. 294-294Conference paper (Other academic)
  • 9.
    Mjösberg, Jenny
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology.
    Berg, Göran
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Ernerudh, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Ekerfelt, Christina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology.
    CD4+ CD25+ regulatory T cells in human pregnancy: Development of a Treg-MLC-ELISPOT suppression assay and indications of paternal specific Tregs2007In: Immunology, ISSN 0019-2805, E-ISSN 1365-2567, Vol. 120, no 4, p. 456-466Article in journal (Refereed)
    Abstract [en]

    The current study was aimed at developing a one-way mixed leucocyte culture-enzyme-linked immunospot (MLC-ELISPOT) assay for the study of CD4 + CD25+ regulatory T (Treg) cells and applying this method in the study of antifetal immune reactions during human pregnancy. Twenty-one pregnant women and the corresponding fathers-to-be, and 10 non-pregnant control women and men, participated in the study. CD4+ CD25+ cells were isolated from peripheral blood mononuclear cells (PBMC) by immunomagnetic selection. Maternal/control PBMC were stimulated with paternal or unrelated PBMC in MLC. Secretion of interleukin-4 (IL-4) and interferon-γ (IFN-γ) from responder cells, with or without the presence of autologous Treg cells, was analysed by ELISPOT. PBMC from pregnant women showed increased secretion of IL-4 compared to controls. In pregnant and non-pregnant controls, Treg cells suppressed IFN-γ reactivity against paternal and unrelated alloantigens. Interestingly, T reg cells suppressed IL-4 secretion against paternal but not unrelated alloantigens during pregnancy. We have successfully developed a model for studying Treg cells in antifetal cytokine reactions during pregnancy. Results indicate that Treg cells contribute to strict regulation of both T helper type 1-like and type 2-like antifetal immune reactions. Interestingly, T helper type 2-like cells specific to unrelated alloantigens are able to escape the suppression of Treg cells, which would allow for IL-4, alongside CD4+ CD25+ Treg cells, to control potentially detrimental IFN-γ reactions during pregnancy. © 2007 Blackwell Publishing Ltd.

  • 10.
    Mjösberg, Jenny
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Berg, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Jenmalm, Maria C.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    FOXP3+ regulatory T cells, T helper 1, T helper 2 and T helper 17 cells in human early pregnancy decidua2010In: Biology of Reproduction, ISSN 0006-3363, E-ISSN 1529-7268, Vol. 82, no 4, p. 698-705Article in journal (Refereed)
    Abstract [en]

    In pregnancy, the decidua is infiltrated by leukocytes promoting fetal development without causing immunological rejection. Murine regulatory T (Treg) cells are known to be important immune regulators at this site. The aim of the study was to characterize the phenotype and origin of Treg cells and determine the quantitative relationship between Treg, T-helper type 1 (TH1), TH2, and TH17 cells in first-trimester human decidua. Blood and decidual CD4+ T cells from 18 healthy first-trimester pregnant women were analyzed for expression of Treg-cell markers (CD25, FOXP3, CD127, CTLA4, and human leukocyte antigen-DR [HLA-DR]), chemokine receptors (CCR4, CCR6, and CXCR3), and the proliferation antigen MKI67 by six-color flow cytometry. Treg cells were significantly enriched in decidua and displayed a more homogenous suppressive phenotype with more frequent expression of FOXP3, HLA-DR, and CTLA4 than in blood. More decidual Treg cells expressed MKI67, possibly explaining their enrichment at the fetal-maternal interface. Using chemokine receptor expression profiles of CCR4, CCR6, and CXCR3 as markers for TH1, TH2, and TH17 cells, we showed that TH17 cells were nearly absent in decidua, whereas TH2-cell frequencies were similar in blood and decidua. CCR6+ TH1 cells, reported to secrete high levels of interferon gamma (IFNG), were fewer, whereas the moderately IFNG-secreting CCR6 TH1 cells were more frequent in decidua compared with blood. Our results point toward local expansion of Treg cells and low occurrence of TH17 cells. Furthermore, local, moderate TH1 activity seems to be a part of normal early pregnancy, consistent with a mild inflammatory environment controlled by Treg cells.

  • 11.
    Mjösberg, Jenny
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences.
    Boij, Roland
    Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Matthiesen, Leif
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Jenmalm, Maria C.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Berg, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Circulating CD4dimCD25highFOXP3+ regulatory T cells in severe early-onset preeclampsiaManuscript (preprint) (Other academic)
    Abstract [en]

    Preeclampsia is an inflammatory condition suggested to involve regulatory CD4+CD25high T helper cell (Treg) disturbances. However, the importance of Tregs in early-onset preeclampsia, associated with increased disease severity and possibly representing a more distinct placental disease, remains unclear. We recently showed that by defining Tregs as CD4dimCD25high cells, the risk of including activated non-Tregs, being more prominent in the circulation during pregnancy, is avoided. The aim of this study was to determine, using updated Treg markers and flow cytometric gating strategies, the frequency and phenotype of circulating Tregs from women with severe early-onset preeclampsia (n=10) as compared with healthy pregnant (n=20) and nonpregnant (n=20) women. The frequency of CD4dimCD25high cells and the expression of FOXP3 was similar in healthy and preeclamptic pregnancy. However, the occurrence of CTLA-4+ and HLA-DR+ cells in the Treg population from preeclamptic women tended to be higher than in healthy pregnant women, indicating alterations in Treg functionality in preeclampsia. Further, the Treg population from healthy pregnant, but not preeclamptic, women tended to be enriched for CCR4+ and CD45R0+ cells as compared with nonpregnant women. In conclusion, although the findings do not support a role for diminished circulating Treg frequency in severe early-onset preeclampsia, the study suggests functional alterations related to Treg suppression, activation and migration mechanisms in this subgroup of preeclamptic women.

  • 12.
    Mjösberg, Jenny
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Berg, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Enrichment of Foxp3(+) T-regs and reduction of T(H)17 cells in human early pregnancy decidua indicate immunosuppressive T cell dominance2009In: in JOURNAL OF REPRODUCTIVE IMMUNOLOGY vol 81, issue 2, 2009, Vol. 81, no 2, p. 147-147Conference paper (Refereed)
    Abstract [en]

    n/a

  • 13.
    Mjösberg, Jenny
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Svensson, J
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences.
    Johansson, E
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences.
    Hellstrom, L
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences.
    Casas, Rosaura
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Boij, R
    Ryhov Hospital.
    Matthiesen, L
    Helsingborg Hospital.
    Jönsson, Jan-Ingvar
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Hematology . Linköping University, Faculty of Health Sciences.
    Berg, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Systemic reduction of functionally suppressive CD4dimCD25highFoxp3+ T-regs in human second trimester pregnancy is induced by progesterone and 17 beta-estradiol2009In: Journal of Reproductive Immunology(ISSN 0165-0378), vol 81, issue 2, 2009, Vol. 81, no 2, p. 160-161Conference paper (Refereed)
    Abstract [en]

    CD4+CD25high regulatory T cells (Tregs) are implicated in maintenance of murine pregnancy. However, reports regarding circulating Treg frequencies in human pregnancy are inconsistent and the functionality and phenotype of these cells in pregnancy have not been clarified. The aim was to determine the frequency, phenotype and function of circulating Tregs in second trimester human pregnancy and the influence of progesterone and 17β-estradiol on Treg phenotype and frequency. Based on expression of Foxp3, CD127 and HLA-DR, as determined by multi-color flow cytometry, we defined a proper CD4dimCD25high Treg population and showed, in contrast to most previous reports, that this population was reduced in second trimester pregnancy. Unexpectedly, Foxp3 expression was decreased in the Treg, as well as in the CD4+ population. These changes could be replicated in an in vitro system resembling the pregnancy hormonal milieu, where 17β-estradiol, and in particular progesterone, induced, in line with the pregnancy situation, a reduction of CD4dimCD25highFoxp3+ cells in PBMC from non-pregnant women. By co-culturing FACS-sorted Tregs and autologous CD4+CD25- responder cells, we showed that Tregs from pregnant women still displayed the same suppressive capacity as non-pregnant women in terms of suppressing IL-2, TNF-α and IFN-γ secretion from responder cells while efficiently producing IL-4 and IL-10. Our findings support the view of hormones, particularly progesterone, as critical regulators of Tregs in pregnancy. Further, we suggest that in the light of the results of this study, early data on circulating Treg frequencies in pregnancy need re-evaluation.

  • 14.
    Mjösberg, Jenny
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Svensson, Judit
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Johansson, Emma
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Hellström, Lotta
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences.
    Casas, Rosaura
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Boij, Roland
    Ryhov Hospital, Jönköping, Sweden.
    Matthiesen, Leif
    Helsingborg Hospital, Helsingborg, Sweden.
    Jönsson, Jan-Ingvar
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Berg, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Systemic reduction of functionally suppressive CD4dimCD25highFoxp3+ Tregs in human second trimester pregnancy is induced by progesterone and 17θ-estradiol2009In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 183, no 1, p. 759-769Article in journal (Refereed)
    Abstract [en]

    CD4+CD25high regulatory T cells (Tregs) are implicated in the maintenance of murine pregnancy. However, reports regarding circulating Treg frequencies in human pregnancy are inconsistent, and the functionality and phenotype of these cells in pregnancy have not been clarified. The aim of this study was to determine the frequency, phenotype, and function of circulating Tregs in the second trimester of human pregnancy and the influence of progesterone and 17β-estradiol on Treg phenotype and frequency. Based on expressions of Foxp3, CD127, and HLA-DR as determined by multicolor flow cytometry, we defined a proper CD4dimCD25high Treg population and showed, in contrast to most previous reports, that this population was reduced in second trimester of pregnancy. Unexpectedly, Foxp3 expression was decreased in the Treg, as well as in the CD4+ population. These changes could be replicated in an in vitro system resembling the pregnancy hormonal milieu, where 17β-estradiol, and in particular progesterone, induced, in line with the pregnancy situation, a reduction of CD4dimCD25highFoxp3+ cells in PBMC from nonpregnant women. By coculturing FACS-sorted Tregs and autologous CD4+CD25 responder cells, we showed that Tregs from pregnant women still displayed the same suppressive capacity as nonpregnant women in terms of suppressing IL-2, TNF-, and IFN- secretion from responder cells while efficiently producing IL-4 and IL-10. Our findings support the view of hormones, particularly progesterone, as critical regulators of Tregs in pregnancy. Furthermore, we suggest that in the light of the results of this study, early data on circulating Treg frequencies in pregnancy need reevaluation.

    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 accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

  • 15.
    Pihl, Mikael
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Chéramy, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Mjösberg, Jenny
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Casas, Rosaura
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Increased expression of regulatory T cell-associated markers in recent-onset diabetic children2011In: Open Journal of Immunology, ISSN 2162-450X, E-ISSN 2162-4526, Vol. 1, no 3, p. 57-64Article in journal (Refereed)
    Abstract [en]

    CD4+CD25hi T cells are thought to be crucial for the maintenance of immunological tolerance to self antigens. In this study, we investigated the frequencies of these cells in the early stage of type 1 diabetes, as well as in a setting of possible pre-diabetic autoimmunity. Hence, the expression of FOXP3, CTLA-4, and CD27 in CD4+ CD25hi T cells was analyzed using flow cytometry in 14 patients with recent onset type 1 diabetes, in 9 at-risk individuals, and 9 healthy individuals with no known risk for type 1 diabetes. Our results show there were no differences in the frequency of CD4+CD25hi cells between groups. However, compared to controls, recent-onset type 1 diabetic patients had higher expression of FOXP3, CTLA-4, and CD27 in CD4+ CD25hi cells from peripheral blood. The median fluorescence intensity of FOXP3 was significantly higher in CD4+CD25hi cells from patients with type 1 diabetes than from controls. Furthermore, a positive correlation between the frequency of FOXP3+ cells and the median fluorescence intensity of FOXP3 was observed among patients with type 1 diabetes. These data suggest that the frequency of CD4+CD25hi FOXP3+ T cells in the periphery is not decreased but rather increased at onset of type 1 diabetes. Thus, functional deficiencies rather than reduced numbers of CD4+CD25hi cells could contribute to the development of type 1 diabetes. 

1 - 15 of 15
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf