Unravelling the T-cell-mediated autoimmune attack on CNS myelin in a new primate EAE model induced with MOG34-56 peptide in incomplete adjuvant

Anwar Jagessar, N Heijmans, ELA Blezer, J Bauer, JH Blokhuis, JAM Wubben, JW Drijfhout, PJ van den Elsen, Jon Laman, Boris Hart

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Abstract

Induction of experimental autoimmune encephalomyelitis (EAE) has been documented in common marmosets using peptide 3456 from human myelin/oligodendrocyte glycoprotein (MOG34-56) 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 MOG3456 displayed high production of IL-17A and specific lysis of MOG3456-pulsed EBV B-lymphoblastoid cells as typical hallmarks. Cytotoxicity was directed at the epitope MOG4048 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 MOG3456, 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 MOG3456/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.
Original languageUndefined/Unknown
Pages (from-to)217-227
Number of pages11
JournalEuropean Journal of Immunology
Volume42
Issue number1
DOIs
Publication statusPublished - 2012

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