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(1/1) 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-1beta, 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.
Hiremath
Meenaxi M
MM
Department of Microbiology and Immunology, University of North Carolina Chapel Hill, NC 27599, USA.
Chen
Vivian S
VS
Suzuki
Kinuko
K
Ting
Jenny P Y
JP
Matsushima
Glenn K
GK
D000818:Animals; D002614:Chelating Agents / Q000633:toxicity; D003471:Cuprizone / Q000633:toxicity; D003593:Cytoplasm / Q000378:metabolism; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology*; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D017628:Microglia / Q000276:immunology / Q000473:pathology; D017434:Protein Structure, Tertiary; D017382:Reactive Oxygen Species / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D002614:Chelating Agents; D000949:Histocompatibility Antigens Class II; D018398:Homeodomain Proteins; D053583:Interleukin-1beta; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C064658:RAG-1 protein; D003471:Cuprizone