Developing and mature oligodendrocytes respond differently to the immune cytokine interferon-gamma

Increasing evidence suggests that the immune cytokine interferon-gamma (IFN-γ) plays a deleterious role in immune-mediated demyelinating disorders. To further understand the effects of IFN-γ on oligodendrocytes, we have compared and quantitated the response of developing and mature oligodendrocytes in vitro to IFN-γ and have observed several differences. Morphological changes and cell death occurred in developing cultures after 2 days in IFN-γ, and in mature oligodendrocytes after 4-7 days. Developing oligodendrocytes underwent significantly increased apoptotic cell death in the presence of IFN-γ, but mature oligodendrocytes exposed to IFN-γ died of necrosis. Prior to morphological changes or cell death in mature oligodendrocytes exposed to IFN-γ, steady-state levels of myelin-specific mRNAs and proteins were reduced. Thus, these results indicate that the sensitivity of oligodendrocytes to IFN-γ is related to the developmental state of the cell. Such information is crucial for understanding the response of oligodendrocytes in immune-mediated demyelinating disorders and during remyelination in these diseases.