MHC class II exacerbates demyelination in vivo independently of T cells

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-A(beta)(-/-) 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-1 beta, TNF-alpha, 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. (C) 2008 Elsevier B.V. All rights reserved.