title: Unravelling the T-cell-mediated autoimmune attack on CNS myelin in a new primate EAE model induced with MOG34-56 peptide in incomplete adjuvant.
abstract: Induction of experimental autoimmune encephalomyelitis (EAE) has been documented in common marmosets using peptide 34-56 from human myelin/oligodendrocyte glycoprotein (MOG(34-56) ) in incomplete Freund's adjuvant (IFA). Here, we report that this EAE model is associated with widespread demyelination of grey and white matter. We performed an in-depth analysis of the specificity, MHC restriction and functions of the activated T cells in the model, which likely cause EAE in an autoantibody-independent manner. T-cell lines isolated from blood and lymphoid organs of animals immunized with MOG(34-56)  displayed high production of IL-17A and specific lysis of MOG(34-56) -pulsed EBV B-lymphoblastoid cells as typical hallmarks. Cytotoxicity was directed at the epitope MOG(40-48)  presented by the non-classical MHC class Ib allele Caja-E, which is orthologue to HLA-E and is expressed in non-inflamed brain. In vivo activated T cells identified by flow cytometry in cultures with MOG(34-56,)  comprised CD4(+) CD56(+)  and CD4(+) CD8(+) CD56(+)  T cells. Furthermore, phenotypical analysis showed that CD4(+) CD8(+) CD56(+)  T cells also expressed CD27, but CD16, CD45RO, CD28 and CCR7 were absent. These results show that, in the MOG34-56/IFA marmoset EAE model, a Caja-E-restricted population of autoreactive cytotoxic T cells plays a key role in the process of demyelination in the grey and white matter.
authors.affiliation: Department of Immunology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: S Anwar
authors.initials: SA
authors.lastname: Jagessar
authors.forename: Nicole
authors.initials: N
authors.lastname: Heijmans
authors.forename: Erwin L A
authors.initials: EL
authors.lastname: Blezer
authors.forename: Jan
authors.initials: J
authors.lastname: Bauer
authors.forename: Jeroen H
authors.initials: JH
authors.lastname: Blokhuis
authors.forename: Jacqueline A M
authors.initials: JA
authors.lastname: Wubben
authors.forename: Jan W
authors.initials: JW
authors.lastname: Drijfhout
authors.forename: Peter J
authors.initials: PJ
authors.lastname: van den Elsen
authors.forename: Jon D
authors.initials: JD
authors.lastname: Laman
authors.forename: Bert A 't
authors.initials: BA
authors.lastname: Hart
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D002144:Callithrix; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology; D020014:K562 Cells; D009103:Multiple Sclerosis / Q000276:immunology*; D009185:Myelin Proteins; D009186:Myelin Sheath / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein; D012313:RNA / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*; D000097625:HLA-E Antigens
chemical_list: D000276:Adjuvants, Immunologic; D015395:Histocompatibility Antigens Class I; D020381:Interleukin-17; D009185:Myelin Proteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D012313:RNA; D000097625:HLA-E Antigens; C571326:MOG protein, human