Journal of Neuroimmune Pharmacology

, Volume 8, Issue 4, pp 1037–1047 | Cite as

Subclinical CNS Inflammation as Response to a Myelin Antigen in Humanized Mice

  • Morad Zayoud
  • Khalifa El Malki
  • Katrin Frauenknecht
  • Bettina Trinschek
  • Luise Kloos
  • Khalad Karram
  • Florian Wanke
  • Julia Georgescu
  • Udo F. Hartwig
  • Clemens Sommer
  • Helmut Jonuleit
  • Ari Waisman
  • Florian C. Kurschus
ORIGINAL ARTICLE

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.

Keywords

EAE Humanized mice MOG NSG moDC 

Abbreviations

GvHD

graft-versus-host disease

NSG

NOD/Scidγc−/−

moDCs

monocyte-derived dendritic cells

MOG

myelin oligodendrocyte glycoprotein

Iba1

ionized calcium binding adaptor molecule 1

Supplementary material

11481_2013_9466_MOESM1_ESM.pdf (4.1 mb)
ESM 1(PDF 4.10 MB)

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Morad Zayoud
    • 1
  • Khalifa El Malki
    • 1
  • Katrin Frauenknecht
    • 2
  • Bettina Trinschek
    • 3
  • Luise Kloos
    • 1
  • Khalad Karram
    • 1
  • Florian Wanke
    • 1
  • Julia Georgescu
    • 4
  • Udo F. Hartwig
    • 5
  • Clemens Sommer
    • 2
  • Helmut Jonuleit
    • 3
  • Ari Waisman
    • 1
  • Florian C. Kurschus
    • 1
  1. 1.Institute for Molecular MedicineUniversity Medical Center of the Johannes Gutenberg-University MainzMainzGermany
  2. 2.Department of NeuropathologyUniversity Medical Center of the Johannes Gutenberg-University MainzMainzGermany
  3. 3.Department of DermatologyUniversity Medical Center of the Johannes Gutenberg-University MainzMainzGermany
  4. 4.SandozKundlAustria
  5. 5.III. Department of Medicine – Hematology, Internal Oncology & PneumologyUniversity Medical Center of the Johannes Gutenberg-University MainzMainzGermany

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