title: Subclinical CNS inflammation as response to a myelin antigen in humanized mice.
abstract: Multiple sclerosis is a demyelinating autoimmune disease of the CNS. Its animal model experimental autoimmune encephalomyelitis is commonly induced by active immunization with myelin antigens. To investigate human immune responses against myelin antigens in vivo we established a new subclinical experimental autoimmune encephalomyelitis model in humanized mice. NOD/Scidγc⁻/⁻ animals were transferred with peripheral blood mononuclear cells from healthy human donors and immunized with myelin antigens in complete Freund's adjuvant and antigen-pulsed autologous dendritic cells. Human T cells recovered from these animals reacted specifically to the soluble domain of myelin oligodendrocyte glycoprotein and secreted proinflammatory cytokines. Furthermore, immunized animals developed subclinical CNS inflammation with infiltrating CD4⁺ and CD8⁺ T cells and production of encephalitogenic cytokines. Thus, this model of myelin-induced CNS inflammation by human T cells may allow testing of new human-specific therapeuticals for multiple sclerosis.
authors: Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Obere Zahlbacher Straße 67, 55131 Mainz, Germany.
authors: Morad
authors: M
authors: Zayoud
authors: Khalifa
authors: K
authors: El Malki
authors: Katrin
authors: K
authors: Frauenknecht
authors: Bettina
authors: B
authors: Trinschek
authors: Luise
authors: L
authors: Kloos
authors: Khalad
authors: K
authors: Karram
authors: Florian
authors: F
authors: Wanke
authors: Julia
authors: J
authors: Georgescu
authors: Udo F
authors: UF
authors: Hartwig
authors: Clemens
authors: C
authors: Sommer
authors: Helmut
authors: H
authors: Jonuleit
authors: Ari
authors: A
authors: Waisman
authors: Florian C
authors: FC
authors: Kurschus
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000633:toxicity*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000633:toxicity*; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
chemical_list: D015703:Antigens, CD; C571326:MOG protein, human; D063308:Myelin-Oligodendrocyte Glycoprotein
references: N Engl J Med. 2006 Sep 7;355(10):1018-28
references: 16908486
references: Nature. 2011 Nov 30;481(7379):81-4
references: 22139420
references: Neurology. 2009 Mar 17;72(11):1008-15
references: 19289741
references: J Immunol. 2005 Apr 15;174(8):5124-31
references: 15814744
references: Clin Immunol. 2008 Mar;126(3):303-14
references: 18096436
references: Blood. 2009 Aug 6;114(6):1263-9
references: 19439734
references: Nat Immunol. 2011 Jun;12(6):560-7
references: 21516112
references: Nature. 1988 Sep 15;335(6187):256-9
references: 2970594
references: Nat Med. 2012 Jan 06;18(1):48-53
references: 22227672
references: Eur J Immunol. 2002 Oct;32(10):2737-47
references: 12355425
references: Proc Natl Acad Sci U S A. 2006 Dec 12;103(50):19057-62
references: 17142321
references: J Neuroimmune Pharmacol. 2011 Mar;6(1):148-57
references: 20532647
references: Blood. 2002 Sep 1;100(5):1734-41
references: 12176895
references: Nat Rev Immunol. 2007 Feb;7(2):118-30
references: 17259968
references: J Immunol. 2004 Mar 1;172(5):2731-8
references: 14978070
references: Am J Pathol. 1988 Mar;130(3):443-54
references: 2450462
references: J Exp Med. 2009 Jun 8;206(6):1303-16
references: 19487416
references: J Clin Invest. 2010 Aug;120(8):2767-81
references: 20628202
references: Nature. 2011 Aug 10;476(7359):214-9
references: 21833088
references: Nat Med. 2012 Jan 06;18(1):66-70
references: 22227675
references: J Exp Med. 2000 Nov 6;192(9):1213-22
references: 11067871
references: Blood. 2009 Apr 2;113(14):3190-7
references: 19196868
references: Eur J Immunol. 1997 Dec;27(12):3135-42
references: 9464798
references: Biochim Biophys Acta. 2011 Feb;1812(2):177-83
references: 20600870
references: J Mol Med (Berl). 1997 Feb;75(2):77-88
references: 9083925
references: Cell. 2008 Aug 22;134(4):577-86
references: 18691745
references: Nat Protoc. 2006;1(4):1947-51
references: 17487181
references: J Allergy Clin Immunol. 2012 Feb;129(2):521-8, 528.e1-7
references: 22078574
references: Nat Immunol. 2011 Jun;12(6):568-75
references: 21516111
references: Brain. 2006 Aug;129(Pt 8):1940-52
references: 16636022
references: Nat Neurosci. 2011 Jul 31;14(9):1142-9
references: 21804537
references: Glia. 2001 Nov;36(2):220-34
references: 11596130
references: Proc Natl Acad Sci U S A. 1990 Oct;87(20):7968-72
references: 1700423
references: Ann Neurol. 2000 Jun;47(6):707-17
references: 10852536
references: Blood. 2003 Oct 1;102(7):2522-31
references: 12791667
references: Trends Mol Med. 2011 Mar;17(3):119-25
references: 21251877
references: Clin Immunol. 2010 Apr;135(1):84-98
references: 20096637
references: Brain. 1999 Nov;122 ( Pt 11):2089-100
references: 10545394
references: Ann Neurol. 2006 Jul;60(1):12-21
references: 16802293
references: J Neurosci. 2009 Nov 25;29(47):14965-79
references: 19940192
references: J Immunol. 1985 Nov;135(5):3128-33
references: 2413113
references: Methods. 2001 Dec;25(4):402-8
references: 11846609
references: Br J Pharmacol. 2011 Oct;164(4):1079-106
references: 21371012
references: Adv Immunol. 2011;110:111-37
references: 21762817
references: Nat Med. 2009 Jun;15(6):626-32
references: 19483694
references: J Exp Med. 2000 Aug 7;192(3):393-404
references: 10934227
references: Cell. 1997 Jun 27;89(7):1021-31
references: 9215625