Fast progression of recombinant human myelin/oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis in marmosets is associated with the activation of MOG34-56-specific cytotoxic T cells.
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.
Kap
Yolanda S
YS
Department of Immunobiology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
Smith
Paul
P
Jagessar
S Anwar
SA
Remarque
Ed
E
Blezer
Erwin
E
Strijkers
Gustav J
GJ
Laman
Jon D
JD
Hintzen
Rogier Q
RQ
Bauer
Jan
J
Brok
Herbert P M
HP
't Hart
Bert A
BA
D000818:Animals; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D015551:Autoimmunity; D001921:Brain / Q000276:immunology / Q000473:pathology; D002144:Callithrix; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D006023:Glycoproteins / Q000276:immunology* / Q000633:toxicity; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology* / Q000633:toxicity; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000276:immunology* / Q000633:toxicity; D011994:Recombinant Proteins / Q000276:immunology / Q000633:toxicity; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*
D001323:Autoantibodies; D006023:Glycoproteins; C571326:MOG protein, human; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D011994:Recombinant Proteins; C517781:myelin oligodendrocyte glycoprotein (34-56); C527289:myelin oligodendrocyte glycoprotein (74-96), human