Experimental autoimmune encephalomyelitis mobilizes neural progenitors from the subventricular zone to undergo oligodendrogenesis in adult mice.

The destiny of the mitotically active cells of the subventricular zone (SVZ) in adult rodents is to migrate to the olfactory bulb, where they contribute to the replacement of granular and periglomerular neurons. However, these adult neural progenitors also can be mobilized in periventricular white matter and triggered to differentiate into astrocytes and oligodendrocytes in response to lysolecithin-induced demyelination. To mimic the environmental conditions of multiple sclerosis, we assessed the proliferation, migration, and differentiation potential of adult SVZ progenitor cells in response to experimental autoimmune encephalomyelitis (EAE) in mice. Inflammation and demyelination were observed in all mouse brains after EAE induction. EAE induced cell proliferation throughout the brain and especially within the lesions. Proliferating cells were neural progenitors, astrocytes, and oligodendrocyte precursors. EAE enhanced the migration of SVZ-derived neural progenitors to the olfactory bulb and triggered their mobilization in the periventricular white matter. The mobilized cells gave rise to neurons, astrocytes, and oligodendrocytes in the olfactory bulb but essentially to astrocytes and oligodendrocytes in the lesioned white matter. Our data indicate that the adult mouse SVZ is a source of newly generated oligodendrocytes and thus may contribute, along with oligodendrocyte precursors, to the replacement of oligodendrocytes in inflammatory demyelinating diseases of the central nervous system such as multiple sclerosis.

Cutting edge: V alpha 14-J alpha 281 NKT cells naturally regulate experimental autoimmune encephalomyelitis in nonobese diabetic mice.

Although deficiencies in the NKT cell population have been observed in multiple sclerosis and mouse strains susceptible to experimental autoimmune encephalomyelitis (EAE), little is known about the function of these cells in CNS autoimmunity. In this work we report that TCR Valpha14-Jalpha281 transgenic nonobese diabetic mice, which are enriched in CD1d-restricted NKT cells, are protected from EAE. The protection is associated with a striking inhibition of Ag-specific IFN-gamma production in the spleen, implying modulation of the encephalitogenic Th1 response. This modulation is independent of IL-4 because IL-4-deficient Valpha14-Jalpha281 mice are still protected against EAE and independent of NKT cell-driven Th1 to Th2 deviation, because no increased autoantigen-specific Th2 response was observed in immunized Valpha14-Jalpha281 transgenic mice. Our findings indicate that enrichment and/or stimulation of CD1d-dependent NKT cells may be used as a novel strategy to treat CNS autoimmunity.