A B Cell-Driven Autoimmune Pathway Leading to Pathological Hallmarks of Progressive Multiple Sclerosis in the Marmoset Experimental Autoimmune Encephalomyelitis Model
The absence of pathological hallmarks of progressive multiple sclerosis (MS) in commonly used rodent models of experimental autoimmune encephalomyelitis (EAE) hinders the development of adequate treatments for progressive disease. Work reviewed here shows that such hallmarks are present in the EAE m...
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| Language: | English |
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Frontiers Media S.A.
2017-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.00804/full |
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| author | Bert A. ’t Hart Bert A. ’t Hart Jordon Dunham Jordon Dunham Bart W. Faber Jon D. Laman Jon D. Laman Jack van Horssen Jan Bauer Yolanda S. Kap |
| author_facet | Bert A. ’t Hart Bert A. ’t Hart Jordon Dunham Jordon Dunham Bart W. Faber Jon D. Laman Jon D. Laman Jack van Horssen Jan Bauer Yolanda S. Kap |
| author_sort | Bert A. ’t Hart |
| collection | DOAJ |
| description | The absence of pathological hallmarks of progressive multiple sclerosis (MS) in commonly used rodent models of experimental autoimmune encephalomyelitis (EAE) hinders the development of adequate treatments for progressive disease. Work reviewed here shows that such hallmarks are present in the EAE model in marmoset monkeys (Callithrix jacchus). The minimal requirement for induction of progressive MS pathology is immunization with a synthetic peptide representing residues 34–56 from human myelin oligodendrocyte glycoprotein (MOG) formulated with a mineral oil [incomplete Freund’s adjuvant (IFA)]. Pathological aspects include demyelination of cortical gray matter with microglia activation, oxidative stress, and redistribution of iron. When the peptide is formulated in complete Freund’s adjuvant, which contains mycobacteria that relay strong activation signals to myeloid cells, oxidative damage pathways are strongly boosted leading to more intensive pathology. The proven absence of immune potentiating danger signals in the MOG34–56/IFA formulation implies that a narrow population of antigen-experienced T cells present in the monkey’s immune repertoire is activated. This novel pathway involves the interplay of lymphocryptovirus-infected B cells with MHC class Ib/Caja-E restricted CD8+ CD56+ cytotoxic T lymphocytes. |
| first_indexed | 2024-12-22T04:01:26Z |
| format | Article |
| id | doaj.art-9d767c2519b74df1b4a717731f226fd8 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-22T04:01:26Z |
| publishDate | 2017-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-9d767c2519b74df1b4a717731f226fd82022-12-21T18:39:44ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-07-01810.3389/fimmu.2017.00804281414A B Cell-Driven Autoimmune Pathway Leading to Pathological Hallmarks of Progressive Multiple Sclerosis in the Marmoset Experimental Autoimmune Encephalomyelitis ModelBert A. ’t Hart0Bert A. ’t Hart1Jordon Dunham2Jordon Dunham3Bart W. Faber4Jon D. Laman5Jon D. Laman6Jack van Horssen7Jan Bauer8Yolanda S. Kap9Department of Immunobiology, Biomedical Primate Research Center, Rijswijk, NetherlandsDepartment of Neuroscience, University of Groningen, University Medical Center, Groningen, NetherlandsDepartment of Immunobiology, Biomedical Primate Research Center, Rijswijk, NetherlandsDepartment of Neuroscience, University of Groningen, University Medical Center, Groningen, NetherlandsDepartment of Parasitology, Biomedical Primate Research Center, Rijswijk, NetherlandsDepartment of Neuroscience, University of Groningen, University Medical Center, Groningen, NetherlandsMS Center Noord-Nederland, Groningen, NetherlandsDepartment of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, NetherlandsDepartment of Neuroimmunology, Brain Research Institute, Medical University Vienna, Vienna, AustriaDepartment of Immunobiology, Biomedical Primate Research Center, Rijswijk, NetherlandsThe absence of pathological hallmarks of progressive multiple sclerosis (MS) in commonly used rodent models of experimental autoimmune encephalomyelitis (EAE) hinders the development of adequate treatments for progressive disease. Work reviewed here shows that such hallmarks are present in the EAE model in marmoset monkeys (Callithrix jacchus). The minimal requirement for induction of progressive MS pathology is immunization with a synthetic peptide representing residues 34–56 from human myelin oligodendrocyte glycoprotein (MOG) formulated with a mineral oil [incomplete Freund’s adjuvant (IFA)]. Pathological aspects include demyelination of cortical gray matter with microglia activation, oxidative stress, and redistribution of iron. When the peptide is formulated in complete Freund’s adjuvant, which contains mycobacteria that relay strong activation signals to myeloid cells, oxidative damage pathways are strongly boosted leading to more intensive pathology. The proven absence of immune potentiating danger signals in the MOG34–56/IFA formulation implies that a narrow population of antigen-experienced T cells present in the monkey’s immune repertoire is activated. This novel pathway involves the interplay of lymphocryptovirus-infected B cells with MHC class Ib/Caja-E restricted CD8+ CD56+ cytotoxic T lymphocytes.http://journal.frontiersin.org/article/10.3389/fimmu.2017.00804/fullmultiple sclerosisanimal modeldemyelinationexperimental autoimmune encephalomyelitisEpstein–Barr virusB cell |
| spellingShingle | Bert A. ’t Hart Bert A. ’t Hart Jordon Dunham Jordon Dunham Bart W. Faber Jon D. Laman Jon D. Laman Jack van Horssen Jan Bauer Yolanda S. Kap A B Cell-Driven Autoimmune Pathway Leading to Pathological Hallmarks of Progressive Multiple Sclerosis in the Marmoset Experimental Autoimmune Encephalomyelitis Model Frontiers in Immunology multiple sclerosis animal model demyelination experimental autoimmune encephalomyelitis Epstein–Barr virus B cell |
| title | A B Cell-Driven Autoimmune Pathway Leading to Pathological Hallmarks of Progressive Multiple Sclerosis in the Marmoset Experimental Autoimmune Encephalomyelitis Model |
| title_full | A B Cell-Driven Autoimmune Pathway Leading to Pathological Hallmarks of Progressive Multiple Sclerosis in the Marmoset Experimental Autoimmune Encephalomyelitis Model |
| title_fullStr | A B Cell-Driven Autoimmune Pathway Leading to Pathological Hallmarks of Progressive Multiple Sclerosis in the Marmoset Experimental Autoimmune Encephalomyelitis Model |
| title_full_unstemmed | A B Cell-Driven Autoimmune Pathway Leading to Pathological Hallmarks of Progressive Multiple Sclerosis in the Marmoset Experimental Autoimmune Encephalomyelitis Model |
| title_short | A B Cell-Driven Autoimmune Pathway Leading to Pathological Hallmarks of Progressive Multiple Sclerosis in the Marmoset Experimental Autoimmune Encephalomyelitis Model |
| title_sort | b cell driven autoimmune pathway leading to pathological hallmarks of progressive multiple sclerosis in the marmoset experimental autoimmune encephalomyelitis model |
| topic | multiple sclerosis animal model demyelination experimental autoimmune encephalomyelitis Epstein–Barr virus B cell |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2017.00804/full |
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