Discrepant effects of human interferon-gamma on clinical and immunological disease parameters in a novel marmoset model for multiple sclerosis.
The core pathogenic process in the common marmoset model of multiple sclerosis (MS) is the activation of memory-like T cells specific for peptide 34 to 56 derived from the extracellular domain of myelin/oligodendrocyte glycoprotein (MOG(34-56)). Immunization with MOG(34-56) in incomplete Freund's adjuvant is a sufficient stimulus for in vivo activation of these T cells, together with the induction of MS-like disease and CNS pathology. Ex vivo functional characteristics of MOG(34-56) specific T cells are specific cytolysis of peptide pulsed target cells and high IL-17A production. To indentify possible functions in this new model of T helper 1 cells, which play a central pathogenic role in MS models induced with complete Freund's adjuvant, we tested the effect of human interferon-γ (IFNγ) administration during disease initiation of the disease (day 0-25) and around the time of disease expression (psd 56-81). The results show a clear modulatory effect of early IFNγ treatment on humoral and cellular autoimmune parameters, but no generalized mitigating effect on the disease course. These results argue against a prominent pathogenic role of T helper 1 cells in this new marmoset EAE model.
Department of Immunobiology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
S Anwar
SA
Jagessar
Bruno
B
Gran
Nicole
N
Heijmans
Jan
J
Bauer
Jon D
JD
Laman
Bert A
BA
't Hart
Cris S
CS
Constantinescu
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D002144:Callithrix; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology* / Q000494:pharmacology; D008297:Male; D009103:Multiple Sclerosis / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*
D007371:Interferon-gamma