We have shown previously the importance of MHC class II for central nervous system remyelination; however, the function of MHC class II during cuprizone-induced demyelination has not been examined. Here, we show that I-Aβ−/− mice exhibit significantly reduced inflammation and demyelination. RAG-1−/− mice are indistinguishable from controls, indicating T cells may not play a role. The role of MHC class II depends on an intact cytoplasmic tail that leads to the production of IL-1β, TNF-α, and nitric oxide, and oligodendrocyte apoptosis. Thus, the function of MHC class II cytoplasmic tail appears to increase microglial proliferation and activation that exacerbates demyelination
