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Keywords:

  • Common marmoset;
  • Cytotoxicity;
  • HLA-E;
  • Oligodendrocytes;
  • Natural killer–cytotoxic T lymphocyte (NK-CTL)

Abstract

Induction of experimental autoimmune encephalomyelitis (EAE) has been documented in common marmosets using peptide 34–56 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 MOG34–56 displayed high production of IL-17A and specific lysis of MOG34–56-pulsed EBV B-lymphoblastoid cells as typical hallmarks. Cytotoxicity was directed at the epitope MOG40–48 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 MOG34–56, 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.