Experimental Autoimmune Encephalomyelitis EAE

EAE is traditionally regarded as a prototypic TH-1 CD4+ T-cell mediated autoimmune disease of the CNS. However, other cells of the immune system play important roles in the neuropathogenesis of this disorder. Defining the precise role of various cell types in EAE is complicated by the diverse and heterogeneous nature of EAE model systems. Recently, a new class of T-cells, TH-17 cells, has been shown to regulate inflammation in EAE. This unique subset of T helper cells produce IL-17 and develops along a pathway that is distinct from that of TH-1 and TH-2 cell differentiation (Park et al., 2005). It has been demonstrated that neutralization of IL-17 with IL-17-receptor-Fc-protein or an IL-17 monoclonal antibody ameliorates the disease course of EAE (Hofstetter et al., 2005). The production of IL-17 requires upstream activation of IL-23, and neutralizing antibodies specific for 

Cellular infiltrate CD4+ T-cells, MOG-specific CD8-P T-cells CD8+ T-cells, CD4+ T-cells, B-cells 

CSF immunology Antibodies to myelin antigens Rarely find antibodies to myelin antigens OCB antigens unknown 

Source Adapted from Lublin (1996) and Sriram and Steiner (2005). 

IL-23 also ameliorate disease progression in EAE (Chen et al., 2006) In addition, EAE is significantly suppressed in lL-17 knockout mice further indicating the importance of lL-17 in the pathogenesis of EAE (Komiyama et al., 2006). 

Cellular nifilfr ate CD4+ T-ceUs, MOG-specific CD 8+ T-cells CD8-I- T-cells, CD4-I- T-cells, B-ceUs 

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In the next phase of the study, transcripts of up-regulated genes granulocyte colony-stimulating factor (G-CSF) and IgG were introduced into a mouse model corranonly used to test potential therapies for experimental autoimmune encephalomyelitis (EAE). Erom microarray analysis, G-CSF was found to be up-regulated in acute MS but not in the chronic state of the disease. Subcutaneous injection of G-CSF prior to induction of EAE prevented onset of the disease in mice. The reversal of EAE by G-CSE has also been described (see Eock, 2002, Reference 40). 

Annexin 1 is up-regulated in multiple sclerosis and in an experimental model of the disease (experimental autoimmune encephalomyelitis-EAE) intracerebroven-tricular administration of annexin 1 proved to be neuroprotective. Annexin 1 is present in both macrophages and astrocytes localised in the lesions (Bolton et al., 1990 Huntinga et al, 1998). In experimental autoimmune neuritis (EAN), a model for human Guillain-Barre syndrome, increased annexin 1 expression was also observed in macrophages and T-cells in the inflamed sciatic nerve (Gold et al., 1999). 

McRae BL, Kennedy MK, Tan LJ, Dal Canto MC, Picha KS, Miller SD (1992) Induction of active and adoptive relapsing experimental autoimmune encephalomyelitis (EAE) using an encephalitogenic epitope of proteolipid protein. J Neuroimmunol 38 229-240. 

In vivo neuroprotection by HDAC inhibition has been linked to upregulation of transcription of antioxidant and growth factor proteins, stimulation of neurogenesis [255], and anti-inflammatory effects [256-258]. An anti-inflammatory effect has been achieved by suppression of microglial activation [259], inhibition of pro-inflammatory cytokine expression [260], or NFkB-mediated inflammatory responses. Treatment with HDAC inhibitors also markedly inhibited ischemia-induced p53 overexpression [261, 262]. In an animal model of multiple sclerosis (experimental autoimmune encephalomyelitis, EAE), treatment with TSA (2, Fig. 1) activated a transcriptional program that culminated in decreased caspase 3 activity [263]. In HD, treatment of Drosophila mutants expressing Htt with the HDAC inhibitors SAHA or TSA (1 or 2, Fig. 1) suppressed neuronal photoreceptor generation [177]. 

Ben-Nun A Cohen IR (1982) Experimental autoimmune encephalomyelitis (EAE) mediated by T cell lines process of selection of lines and characterization of the cells. J Immunol, 129(1) 303-308. 

Fig. 4.12 Results of a quantitative ultrasound study in experimental autoimmune encephalomyelitis (EAE) rats. Application of ICAM-1-targeted microparticles results in a highly significant...

Fig. 7.9 Quantitative results of SPAQ investigations in accordance to the workflow described in Fig. 7.8. Bars show mean values and standard deviations (n = 4) of SAE signals expressed as acoustic counts of ICAM-1 targeted ultrasound contrast agents at the blood brain barrier. The values are registered from the entire brain of healthy rats and rats with adoptive transfer experimental autoimmune encephalomyelitis (EAE-rats), respectively. For further experimental details please refer to Reinhardt et al [40]. Based on different investigations five important theses could be verified ...

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