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* Department of Immunobiology,
Department of Parasitology, and
Department of Animal Science, Biomedical Primate Research Centre, Rijswijk, The Netherlands;
Department of Immunology,
¶ Department of Neurology, and
|| Multiple Sclerosis Centre ErasMS, Erasmus Medical Centre, Rotterdam, The Netherlands;
# Imaging Science Institute, University Medical Center Utrecht, Utrecht, The Netherlands;
** Biomedical Nuclear Magnetic Resonance Group, Department of Medical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands; and
Brain Research Institute, University of Vienna, Vienna, Austria
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 MOG34–56 and MOG74–96. MOG34–56 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 MOG74–96-immunized monkeys, weak T cell responses against MOG34–56 and low grade CNS pathology were detected. When these cases received a booster immunization with MOG34–56 in IFA, full-blown EAE developed. MOG34–56-reactive T cells expressed CD3, CD4, or CD8 and CD56, but not CD16. Moreover, MOG34–56-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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by Dutch Multiple Sclerosis Research Foundation Grants 00-417, 02-490, and Program Grant 2000-2004. This study was financially supported by an unbiased grant from Biotempt B. V., Koekange, The Netherlands.
2 Y.S.K., P.S., and S.A.J. contributed equally to this work.
3 H.P.M.B. and B.A.’t.H. share senior authorship.
4 Address correspondence and reprint requests to Dr. Bert A. ’t Hart, Department of Immunobiology, Biomedical Primate Research Centre, P.O. Box 3306, 2280 GH Rijswijk, The Netherlands. E-mail address: hart{at}bprc.nl
5 Abbreviations used in this paper: MS, multiple sclerosis; ALN, axillary lymph node; CLN, cervical lymph node; EAE, experimental autoimmune encephalomyelitis; ILN, inguinal lymph node; MBP, myelin basic protein; MNC, mononuclear cell; MOG, myelin/oligodendrocyte glycoprotein; MR, magnetic resonance; MRI, magnetic resonance imaging; NAWM, normal appearing white matter; PLP, proteolipid protein; psd, post sensitization day; SI, stimulation index; TCL, T cell line; T2W, T2 weighted; WM, white matter.
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