Background: Dendritic cells (DCs) rendered suppressive by treatment with mitomycin C and loaded with the\nautoantigen myelin basic protein demonstrated earlier their ability to prevent experimental autoimmune encephalomyelitis\n(EAE), the animal model for multiple sclerosis (MS). This provides an approach for prophylactic vaccination\nagainst autoimmune diseases. For clinical application such DCs are difficult to generate and autoantigens hold the risk\nof exacerbating the disease.\nMethods: We replaced DCs by peripheral mononuclear cells and myelin autoantigens by glatiramer acetate (Copaxone\n�®), a drug approved for the treatment of MS. Spleen cells were loaded with Copaxone�®, incubated with mitomycin\nC (MICCop) and injected into mice after the first bout of relapsing-remitting EAE. Immunosuppression mediated by\nMICCop was investigated in vivo by daily assessment of clinical signs of paralysis and in in vitro restimulation assays of\nperipheral immune cells. Cytokine profiling was performed by enzyme-linked immunosorbent assay (ELISA). Migration\nof MICCop cells after injection was examined by biodistribution analysis of 111Indium-labelled MICCop. The number\nand inhibitory activity of CD4+CD25+FoxP3+ regulatory T cells were analysed by histology, flow cytometry and in vitro\nmixed lymphocyte cultures. In order to assess the specificity of MICCop-induced suppression, treated EAE mice were\nchallenged with the control protein ovalbumin. Humoral and cellular immune responses were then determined by\nELISA and in vitro antigen restimulation assay.\nResults: MICCop cells were able to inhibit the harmful autoreactive T-cell response and prevented mice from further\nrelapses without affecting general immune responses. Administered MICCop migrated to various organs leading to an\nincreased infiltration of the spleen and the central nervous system with CD4+CD25+FoxP3+ cells displaying a suppressive\ncytokine profile and inhibiting T-cell responses.\nConclusion: We describe a clinically applicable cell therapeutic approach for controlling relapses in autoimmune\nencephalomyelitis by specifically silencing the deleterious autoimmune response.
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