| Abstrakt: |
Multiple sclerosis (MS) can be divided into 4 clinical forms: relapsing‐remitting (RR), primary progressive (PP), secondary progressive (SP), and progressive relapsing (PR). Since PP‐MS is notably different from the other forms of MS, both clinically and pathologically, the question arises whether PP‐MS is immunologically similar to the other forms. The pathogenesis of the PP‐MS remains unclear, partly due to a lack of highly relevant animal models. Using an encephalitogenic peptide from myelin oligodendrocyte glycoprotein (MOG)92–106, we have established animal models that mimic different forms of MS in 2 strains of H‐2smice, SJL/J and A.SW. We induced experimental allergic encephalomyelitis (EAE) using MOG92‐106in the presence or absence of supplemental Bordetella pertussis (BP). Although, SJL/J mice developed RR‐EAE whether BP was given or not, A.SW mice developed PP‐EAE without BP and SP‐EAE with BP. Histologically, SJL/J mice developed mild demyelinating disease with T cell infiltration, while A.SW mice developed large areas of plaque‐like demyelination with immunoglobulin deposition and neutrophil infiltration, but with minimal T cell infiltration. In A.SW mice without BP, high titer serum anti‐MOG antibody was detected and the anti‐MOG IgG2a/IgG1 ratio correlated with survival times of mice. We hypothesized that, in A.SW mice, a Th2 response favors production of myelinotoxic antibodies, leading to progressive forms with early death. Our new models indicate that a single encephalitogen could induce either RR‐, PP‐, or SP‐ forms of demyelinating disease in hosts with immunologically different humoral immune responses. |
