title: Immune profile of an atypical EAE model in marmoset monkeys immunized with recombinant human myelin oligodendrocyte glycoprotein in incomplete Freund's adjuvant.
abstract: 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).
  
  
  METHODS
  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.
authors.affiliation: Department of Immunobiology, Biomedical Primate Research Centre, P.O. Box 3306, 2280, GH, Rijswijk, The Netherlands. jagessar@bprc.nl.|ErasMS Centre, Erasmus Medical Center, Rotterdam, The Netherlands. jagessar@bprc.nl.
authors.forename: S Anwar
authors.initials: SA
authors.lastname: Jagessar
authors.affiliation: Department of Immunobiology, Biomedical Primate Research Centre, P.O. Box 3306, 2280, GH, Rijswijk, The Netherlands.
authors.forename: Nicole
authors.initials: N
authors.lastname: Heijmans
authors.affiliation: Image Sciences Institute, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Erwin L A
authors.initials: EL
authors.lastname: Blezer
authors.affiliation: Center for Brain Research, Medical University of Vienna, Vienna, Austria. jan.bauer@meduniwien.ac.at.
authors.forename: Jan
authors.initials: J
authors.lastname: Bauer
authors.affiliation: Department of Neurology, University of Regensburg, Regensburg, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Weissert
authors.affiliation: Department of Immunobiology, Biomedical Primate Research Centre, P.O. Box 3306, 2280, GH, Rijswijk, The Netherlands. hart@bprc.nl.|ErasMS Centre, Erasmus Medical Center, Rotterdam, The Netherlands. hart@bprc.nl.|Department of Neuroscience, University of Groningen, Groningen, The Netherlands. hart@bprc.nl.
authors.forename: Bert A
authors.initials: BA
authors.lastname: 't Hart
mesh_terms: D000818:Animals; D000906:Antibodies / Q000097:blood; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002144:Callithrix; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000097:blood / Q000235:genetics; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D005260:Female; D005620:Freund's Adjuvant / Q000009:adverse effects / Q000276:immunology*; D006801:Humans; D007114:Immunization / Q000009:adverse effects; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology; D008055:Lipids / Q000009:adverse effects / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D009186:Myelin Sheath / Q000378:metabolism / Q000473:pathology; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000009:adverse effects / Q000276:immunology*; D010455:Peptides / Q000009:adverse effects / Q000276:immunology; D011994:Recombinant Proteins / Q000009:adverse effects / Q000276:immunology; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000906:Antibodies; D016207:Cytokines; D008055:Lipids; C571326:MOG protein, human; D063308:Myelin-Oligodendrocyte Glycoprotein; D010455:Peptides; D011994:Recombinant Proteins; C114843:incomplete Freund's adjuvant; D005620:Freund's Adjuvant