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Attenuation of Experimental Autoimmune Encephalomyelitis in a Common Marmoset Model by Dendritic Cell-Modulating Anti-ICAM-1 Antibody, MD-3

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Abstract

MD-3 is a novel anti-human ICAM-1 monoclonal antibody that induces T cell tolerance in humanized mice via modulation of dendritic cell differentiation and efficiently suppresses the development of collagen-induced arthritis. This effect has also been observed in xenograft rejection in nonhuman primates, where grafts survived for more than 2.5 years following MD-3 administration. Here, we show that MD-3 can attenuate experimental autoimmune encephalomyelitis (EAE) that was induced in common marmoset monkeys by immunization with human myelin oligodendrocyte glycoproteins. MD-3 administration was initiated 1 week after immunization and efficiently delayed the development of EAE phenotypes, although the disease was not completely prevented. Based on the results of histopathological examination, MD-3 treatment greatly suppressed total inflammation with respect to demyelination, as well as T cell and microglial infiltration in the brain. However, the antibody response against myelin oligodendrocyte glycoprotein was not suppressed with this treatment protocol. These observations suggest that the MD-3 antibody has beneficial effects on the treatment of EAE via the suppression of T cell-mediated cellular responses.

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Acknowledgements

Special thanks are due to professor Seong Hoe Park of Seoul National University College of Medicine for his innumerable contributions, including many helpful discussions and continued advice during all experimental processes as well as reading the entire manuscript and providing comments.

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Author notes

  1. Soon-Tae Lee and Seung Pyo Park contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, Seoul National University Hospital, Seoul, Republic of Korea

    Soon-Tae Lee

  2. Neuroscience Research Institute, Seoul National University Medical Research Center, Seoul, Republic of Korea

    Seung Pyo Park & Young Ho Suh

  3. Graduate Course of Translational Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea

    Hi-Jung Park, Jae-Il Lee & Kyeong Cheon Jung

  4. Alizée Pathology, Thurmont, MD, 21788, USA

    Joan R. Wicks

  5. Transplantation Research Institute, Seoul National University Medical Research Center, Seoul, Republic of Korea

    Jae-Il Lee & Kyeong Cheon Jung

  6. Department of Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea

    Jae-Il Lee

  7. Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea

    Young Ho Suh

  8. Department of Pathology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea

    Kyeong Cheon Jung

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  1. Soon-Tae Lee
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Correspondence to Kyeong Cheon Jung.

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Lee, ST., Park, S.P., Park, HJ. et al. Attenuation of Experimental Autoimmune Encephalomyelitis in a Common Marmoset Model by Dendritic Cell-Modulating Anti-ICAM-1 Antibody, MD-3. Mol Neurobiol 56, 5136–5145 (2019). https://doi.org/10.1007/s12035-018-1438-5

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  • DOI: https://doi.org/10.1007/s12035-018-1438-5

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