Unravelling the T-cell-mediated autoimmune attack on CNS myelin in a new primate EAE model induced with MOG 34-56 peptide in incomplete adjuvant
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 MOG34-56displayed 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 MOG40-48presented 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.
|Keywords||Common marmoset, Cytotoxicity, HLA-E, Natural killer-cytotoxic T lymphocyte (NK-CTL), Oligodendrocytes|
|Persistent URL||dx.doi.org/10.1002/eji.201141863, hdl.handle.net/1765/31943|
Jagessar, S.A., Heijmans, N., Blezer, E., Bauer, J., Blokhuis, J.H., & Wubben, J.A.M.. (2012). Unravelling the T-cell-mediated autoimmune attack on CNS myelin in a new primate EAE model induced with MOG 34-56 peptide in incomplete adjuvant. European Journal of Immunology, 42(1), 217–227. doi:10.1002/eji.201141863