MYELIN OLIGODENDROCYTE GLYCOPROTEIN-INDUCED AUTOIMMUNE ENCEPHALOMYELITIS IS CHRONIC RELAPSING IN PERFORIN KNOCKOUT MICE, BUT MONOPHASIC IN FAS-DEFICIENT AND FAS LIGAND-DEFICIENT LPR AND GLD MICE/

The expression and action of Fas/Fas ligand (FasL) in multiple scleros is has been postulated as a major pathway leading to inflammatory demy elination. To formally test this hypothesis, C57BL/6-lpr and -gld mice , which due to gene mutation express Fas and Fast in an inactive form, were immunized with myelin oligodendrocyte glycoprotein peptide(35-55 ). Whereas in wild-type C57BL/6 mice, experimental autoimmune encephal omyelitis (EAE), was chronic/relapsing, EAE in lpr and gld mice was ch aracterized by a lower incidence of disease and a monophasic course. T his contrasts with C57BL/6 perforin knockout mice, which showed the mo st severe form of EAE of all mouse strains tested, the course being ch ronic relapsing. The difference noted cannot be attributed to an invol vement of Fast in oligodendrocyte damage since oligodendrocytes are in sensitive to Fast-mediated cytotoxicity in vitro, and since in the acu te phase of EAE gld mice also show CD4(+) T cell infiltrates with asso ciated demyelination in brain and spinal cord. Unlike oligodendrocytes , astrocytes were killed by Fast in vitro. It remains to be establishe d whether this latter finding explains the different disease course of lpr and gld mice compared to wild-type and perforin knockout mice.