.............................................................................................................................................. 68 Introduction ......................................................................................................................................... 69 Results ................................................................................................................................................. 70 EAE induction in immunoproteasome-deficient mice. ................................................................... 70 An LMP7-selective inhibitor prevents symptoms of EAE. ............................................................... 70 LMP7 inhibition prevents brain and spinal cord inflammation. ...................................................... 72 Therapeutic treatment with ONX 0914 inhibits progression of MOG35-55-induced EAE. ................ 75 ONX 0914 blocks differentiation to autoreactive T cells. ................................................................ 77 ONX 0914 reduces clinical symptoms in the PLP139-15-induced relapsing-remitting EAE model in SJL/J Mice. ....................................................................................................................................... 77 Discussion ............................................................................................................................................ 79 Material and Methods ......................................................................................................................... 82 Supplementary information ................................................................................................................ 87 CHAPTER III: LCMV-INDUCED MENINGITIS ............................................................................ 88 1. Inhibition and deficiency of the immunoproteasome subunit LMP7 attenuates LCMVinduced meningitis ..................................................................................................................... 88 Abstract ............................................................................................................................................... 89.............................................................................................................................................. 89