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

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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.

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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

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Acknowledgments

We thank André Heinen, Petra Adams and Nicole Roder for excellent technical support. This work was supported by the DFG via TR128 to FK (TP A03) and to AW (TP A07).

Disclosure of conflicts of interest

The authors have no conflict of interest. The manuscript contains a part of the medical thesis of Morad Zayoud.

Author information

Author notes

  1. Julia Georgescu

    Present address: Sandoz, Kundl, Austria

Authors and Affiliations

  1. Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Obere Zahlbacher Straße 67, 55131, Mainz, Germany

    Morad Zayoud, Khalifa El Malki, Luise Kloos, Khalad Karram, Florian Wanke, Ari Waisman & Florian C. Kurschus

  2. Department of Neuropathology, University Medical Center of the Johannes Gutenberg-University Mainz, 55131, Mainz, Germany

    Katrin Frauenknecht & Clemens Sommer

  3. Department of Dermatology, University Medical Center of the Johannes Gutenberg-University Mainz, 55131, Mainz, Germany

    Bettina Trinschek & Helmut Jonuleit

  4. III. Department of Medicine – Hematology, Internal Oncology & Pneumology, University Medical Center of the Johannes Gutenberg-University Mainz, 55131, Mainz, Germany

    Udo F. Hartwig

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  1. Morad Zayoud
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Corresponding author

Correspondence to Florian C. Kurschus.

Additional information

Khalifa El Malki and Katrin Frauenknecht contributed equally.

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Zayoud, M., El Malki, K., Frauenknecht, K. et al. Subclinical CNS Inflammation as Response to a Myelin Antigen in Humanized Mice. J Neuroimmune Pharmacol 8, 1037–1047 (2013). https://doi.org/10.1007/s11481-013-9466-4

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