title: Induction of progressive demyelinating autoimmune encephalomyelitis in common marmoset monkeys using MOG34-56 peptide in incomplete freund adjuvant.
abstract: Experimental autoimmune encephalomyelitis in the neotropical primate common marmoset (Callithrix jacchus) is a relevant autoimmune animal model of multiple sclerosis. T cells specific for peptide 34 to 56 of myelin/oligodendrocyte glycoprotein (MOG34-56) have a central pathogenic role in this model. The aim of this study was to assess the requirement for innate immune stimulation for activation of this core pathogenic autoimmune mechanism. Marmoset monkeys were sensitized against synthetic MOG34-56 peptide alone or in combination with the nonencephalitogenic peptide MOG74-96 formulated in incomplete Freund adjuvant, which lacks microbial components. Experimental autoimmune encephalomyelitis development was recorded by monitoring neurological signs, brain magnetic resonance imaging, and longitudinal profiling of cellular and humoral immune parameters. All monkeys developed autoimmune inflammatory/demyelinating central nervous system disease characterized by massive brain and spinal cord demyelinating white matter lesions with activated macrophages and CD3+ T cells. Immune profiling ex vivo demonstrated the activation of mainly CD3+CD4+/8+CD56+ T cells against MOG34-56. Upon ex vivo stimulation, these T cells produced more interleukin 17A compared with TH1 cytokines (e.g. interferon-gamma) and displayed peptide-specific cytolytic activity. These results indicate that the full spectrum of marmoset experimental autoimmune encephalomyelitis can be induced by sensitization against a single MOG peptide in incomplete Freund adjuvant lacking microbial compounds for innate immune activation and by eliciting antigen-specific T-cell cytolytic activity.
authors.affiliation: Department of Immunobiology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: S Anwar
authors.initials: SA
authors.lastname: Jagessar
authors.forename: Yolanda S
authors.initials: YS
authors.lastname: Kap
authors.forename: Nicole
authors.initials: N
authors.lastname: Heijmans
authors.forename: Nikki
authors.initials: N
authors.lastname: van Driel
authors.forename: Linda
authors.initials: L
authors.lastname: van Straalen
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Bajramovic
authors.forename: Herbert P M
authors.initials: HP
authors.lastname: Brok
authors.forename: Erwin L A
authors.initials: EL
authors.lastname: Blezer
authors.forename: Jan
authors.initials: J
authors.lastname: Bauer
authors.forename: Jon D
authors.initials: JD
authors.lastname: Laman
authors.forename: Bert A
authors.initials: BA
authors.lastname: 't Hart
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D001921:Brain / Q000276:immunology / Q000473:pathology; D040502:Calgranulin B / Q000378:metabolism; D002144:Callithrix; D002461:Cell Line, Transformed; D016207:Cytokines / Q000378:metabolism; D020278:Demyelinating Autoimmune Diseases, CNS / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D005434:Flow Cytometry / Q000379:methods; D005620:Freund's Adjuvant / Q000737:chemistry*; D006023:Glycoproteins / Q000494:pharmacology*; D006801:Humans; D007113:Immunity, Innate; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008279:Magnetic Resonance Imaging / Q000379:methods; D018991:Myelin Proteolipid Protein / Q000378:metabolism; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000494:pharmacology*; D013116:Spinal Cord / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D001323:Autoantibodies; D040502:Calgranulin B; D016207:Cytokines; D006023:Glycoproteins; D018991:Myelin Proteolipid Protein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C517781:myelin oligodendrocyte glycoprotein (34-56); D005620:Freund's Adjuvant