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Immune profile of an atypical EAE model in marmoset monkeys immunized with recombinant human myelin oligodendrocyte glycoprotein in incomplete Freund’s adjuvant
BACKGROUND: Experimental autoimmune encephalomyelitis (EAE) in the common marmoset monkey (Callithrix jacchus) is a relevant preclinical model for translational research into immunopathogenic mechanisms operating in multiple sclerosis (MS). Prior studies showed a core pathogenic role of T and B cell...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4574133/ https://www.ncbi.nlm.nih.gov/pubmed/26377397 http://dx.doi.org/10.1186/s12974-015-0378-5 |
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author | Jagessar, S. Anwar Heijmans, Nicole Blezer, Erwin L A Bauer, Jan Weissert, Robert ‘t Hart, Bert A. |
author_facet | Jagessar, S. Anwar Heijmans, Nicole Blezer, Erwin L A Bauer, Jan Weissert, Robert ‘t Hart, Bert A. |
author_sort | Jagessar, S. Anwar |
collection | PubMed |
description | BACKGROUND: Experimental autoimmune encephalomyelitis (EAE) in the common marmoset monkey (Callithrix jacchus) is a relevant preclinical model for translational research into immunopathogenic mechanisms operating in multiple sclerosis (MS). Prior studies showed a core pathogenic role of T and B cells specific for myelin oligodendrocyte glycoprotein (MOG). However, in those studies, the quality of the response against MOG epitopes was strongly biased by bacterial antigens in the complete Freund’s adjuvant (CFA), in which the immunizing recombinant human (rh) MOG protein had been formulated. In response to the need of a more refined EAE model, we have tested whether disease could also be induced with rhMOG in incomplete Freund’s adjuvant (IFA). METHOD: Marmosets were immunized with rhMOG emulsified in IFA in the dorsal skin. Monkeys that did not develop neurological deficit were given booster immunizations at 28-day interval with the same antigen preparation. In a second experiment, three marmoset twin pairs were sensitized against MOG peptides in IFA to study a possibility for suppressive activity towards pathogenic T cells directed against the encephalitogenic epitope MOG40-48. RESULTS: Despite the absence of strong danger signals in the rhMOG/IFA inoculum, all monkeys developed clinically evident EAE symptoms. Moreover, in all monkeys, demyelinated lesions were present in the white matter and in two cases also in the cortical grey matter. Immune profiling at height of the disease showed a dominant T cell response against the overlapping peptides 14–36 and 24–46, but reactivity against the pathogenically most relevant peptide 34–56 was conspicuously absent. In the second experiment, there was an indication for a possible suppressive mechanism. CONCLUSIONS: Immunization of marmoset monkeys with rhMOG in IFA elicits clinical EAE in all animals. Moreover, rhMOG contains pathogenic and regulatory epitopes, but the pathogenic hierarchy of rhMOG epitopes is strongly influenced by the adjuvant in which the protein is formulated. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12974-015-0378-5) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4574133 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-45741332015-09-19 Immune profile of an atypical EAE model in marmoset monkeys immunized with recombinant human myelin oligodendrocyte glycoprotein in incomplete Freund’s adjuvant Jagessar, S. Anwar Heijmans, Nicole Blezer, Erwin L A Bauer, Jan Weissert, Robert ‘t Hart, Bert A. J Neuroinflammation Research BACKGROUND: Experimental autoimmune encephalomyelitis (EAE) in the common marmoset monkey (Callithrix jacchus) is a relevant preclinical model for translational research into immunopathogenic mechanisms operating in multiple sclerosis (MS). Prior studies showed a core pathogenic role of T and B cells specific for myelin oligodendrocyte glycoprotein (MOG). However, in those studies, the quality of the response against MOG epitopes was strongly biased by bacterial antigens in the complete Freund’s adjuvant (CFA), in which the immunizing recombinant human (rh) MOG protein had been formulated. In response to the need of a more refined EAE model, we have tested whether disease could also be induced with rhMOG in incomplete Freund’s adjuvant (IFA). METHOD: Marmosets were immunized with rhMOG emulsified in IFA in the dorsal skin. Monkeys that did not develop neurological deficit were given booster immunizations at 28-day interval with the same antigen preparation. In a second experiment, three marmoset twin pairs were sensitized against MOG peptides in IFA to study a possibility for suppressive activity towards pathogenic T cells directed against the encephalitogenic epitope MOG40-48. RESULTS: Despite the absence of strong danger signals in the rhMOG/IFA inoculum, all monkeys developed clinically evident EAE symptoms. Moreover, in all monkeys, demyelinated lesions were present in the white matter and in two cases also in the cortical grey matter. Immune profiling at height of the disease showed a dominant T cell response against the overlapping peptides 14–36 and 24–46, but reactivity against the pathogenically most relevant peptide 34–56 was conspicuously absent. In the second experiment, there was an indication for a possible suppressive mechanism. CONCLUSIONS: Immunization of marmoset monkeys with rhMOG in IFA elicits clinical EAE in all animals. Moreover, rhMOG contains pathogenic and regulatory epitopes, but the pathogenic hierarchy of rhMOG epitopes is strongly influenced by the adjuvant in which the protein is formulated. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12974-015-0378-5) contains supplementary material, which is available to authorized users. BioMed Central 2015-09-17 /pmc/articles/PMC4574133/ /pubmed/26377397 http://dx.doi.org/10.1186/s12974-015-0378-5 Text en © Jagessar et al. 2015 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Jagessar, S. Anwar Heijmans, Nicole Blezer, Erwin L A Bauer, Jan Weissert, Robert ‘t Hart, Bert A. Immune profile of an atypical EAE model in marmoset monkeys immunized with recombinant human myelin oligodendrocyte glycoprotein in incomplete Freund’s adjuvant |
title | Immune profile of an atypical EAE model in marmoset monkeys immunized with recombinant human myelin oligodendrocyte glycoprotein in incomplete Freund’s adjuvant |
title_full | Immune profile of an atypical EAE model in marmoset monkeys immunized with recombinant human myelin oligodendrocyte glycoprotein in incomplete Freund’s adjuvant |
title_fullStr | Immune profile of an atypical EAE model in marmoset monkeys immunized with recombinant human myelin oligodendrocyte glycoprotein in incomplete Freund’s adjuvant |
title_full_unstemmed | Immune profile of an atypical EAE model in marmoset monkeys immunized with recombinant human myelin oligodendrocyte glycoprotein in incomplete Freund’s adjuvant |
title_short | Immune profile of an atypical EAE model in marmoset monkeys immunized with recombinant human myelin oligodendrocyte glycoprotein in incomplete Freund’s adjuvant |
title_sort | immune profile of an atypical eae model in marmoset monkeys immunized with recombinant human myelin oligodendrocyte glycoprotein in incomplete freund’s adjuvant |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4574133/ https://www.ncbi.nlm.nih.gov/pubmed/26377397 http://dx.doi.org/10.1186/s12974-015-0378-5 |
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