Fast progression of recombinant human myelin/oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis, in marmosets is associated with the activation of MOG(34-56)-specific cytotoxic T cells

Yolanda Kap, P Smith, Anwar Jagessar, E Remarque, E Blezer, GJ Strijkers, Jon Laman, Rogier Hintzen, J Bauer, HPM Brok, Boris Hart

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The recombinant human (rh) myelin/oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) model in the common marmoset is characterized by 100% disease incidence, a chronic disease course, and a variable time interval between immunization and neurological impairment. We investigated whether monkeys with fast and slow disease progression display different anti-MOG T or B cell responses and analyzed the underlying pathogenic mechanism(s). The results show that fast progressor monkeys display a significantly wider specificity diversification of anti-MOG T cells at necropsy than slow progressors, especially against MOG(34-56) and MOG(74-96). MOG(34-56) emerged as a critical encephalitogenic peptide, inducing severe neurological disease and multiple lesions with inflammation, demyelination, and axonal injury in the CNS. Although EAE was not observed in MOG(74-96)-immunized monkeys, weak T cell responses against MOG(34-56) and low grade CNS pathology were detected. When these cases received a booster immunization with MOG(34-56) in IFA, full-blown EAE developed. MOG(34-56)-reactive T cells expressed CD3, CD4, or CD8 and CD56, but not CD16. Moreover, MOG(34-56)-specific T cell lines displayed specific cytotoxic activity against peptide-pulsed B cell lines. The phenotype and cytotoxic activity suggest that these cells are NK-CTL. These results support the concept that cytotoxic cells may play a role in the pathogenesis of multiple sclerosis.
Original languageUndefined/Unknown
Pages (from-to)1326-1337
Number of pages12
JournalJournal of Immunology
Volume180
Issue number3
Publication statusPublished - 2008

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