ORIGINAL ARTICLE

Journal of Neuroimmune Pharmacology

, Volume 8, Issue 4, pp 1037-1047

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

  • Morad ZayoudAffiliated withInstitute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz
  • , Khalifa El MalkiAffiliated withInstitute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz
  • , Katrin FrauenknechtAffiliated withDepartment of Neuropathology, University Medical Center of the Johannes Gutenberg-University Mainz
  • , Bettina TrinschekAffiliated withDepartment of Dermatology, University Medical Center of the Johannes Gutenberg-University Mainz
  • , Luise KloosAffiliated withInstitute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz
  • , Khalad KarramAffiliated withInstitute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz
  • , Florian WankeAffiliated withInstitute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz
  • , Julia GeorgescuAffiliated withSandoz
  • , Udo F. HartwigAffiliated withIII. Department of Medicine – Hematology, Internal Oncology & Pneumology, University Medical Center of the Johannes Gutenberg-University Mainz
    • , Clemens SommerAffiliated withDepartment of Neuropathology, University Medical Center of the Johannes Gutenberg-University Mainz
    • , Helmut JonuleitAffiliated withDepartment of Dermatology, University Medical Center of the Johannes Gutenberg-University Mainz
    • , Ari WaismanAffiliated withInstitute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz
    • , Florian C. KurschusAffiliated withInstitute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz Email author 

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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