TY - JOUR
T1 - 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
AU - Kap, Yolanda
AU - Smith, P
AU - Jagessar, Anwar
AU - Remarque, E
AU - Blezer, E
AU - Strijkers, GJ
AU - Laman, Jon
AU - Hintzen, Rogier
AU - Bauer, J
AU - Brok, HPM
AU - Hart, Boris
PY - 2008
Y1 - 2008
N2 - 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.
AB - 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.
M3 - Article
SN - 0022-1767
VL - 180
SP - 1326
EP - 1337
JO - Journal of Immunology
JF - Journal of Immunology
IS - 3
ER -