Blockade of tumour necrosis factor‐α in experimental autoimmune encephalomyelitis reveals differential effects on the antigen‐specific immune response and central nervous system histopathology |
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Authors: | H. Batoulis M. S. Recks F. O. Holland F. Thomalla R. O. Williams S. Kuerten |
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Affiliation: | 1. Department of Anatomy I, University of Cologne, , Cologne, Germany;2. Kennedy Institute of Rheumatology, University of Oxford, , London, UK;3. Department of Anatomy and Cell Biology, University of Wuerzburg, , Wuerzburg, Germany |
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Abstract: | In various autoimmune diseases, anti‐tumour necrosis factor (TNF)‐α treatment has been shown to reduce both clinical disease severity and T helper type 1 (Th1)1/Th17 responses. In experimental autoimmune encephalomyelitis (EAE), however, the role of TNF‐α has remained unclear. Here, C57BL/6 mice were immunized with myelin oligodendrocyte glycoprotein (MOG) peptide 35–55 and treated with anti‐TNF‐α, control antibody or vehicle. The clinical disease course, incidence and severity were assessed. On day 20 after immunization the antigen‐specific Th1/Th17 response was evaluated by enzyme‐linked immunospot (ELISPOT) in spleen and central nervous system (CNS). Also, the extent of spinal cord histopathology was analysed on semi‐ and ultrathin sections. Our results demonstrate that anti‐TNF‐α treatment reduced the incidence and delayed the onset of EAE, but had no effect on disease severity once EAE had been established. Whereas anti‐TNF‐α treatment induced an increase in splenic Th1/Th17 responses, there was no effect on the number of antigen‐specific Th1/Th17 cells in the spinal cord. Accordingly, the degree of CNS histopathology was comparable in control and anti‐TNF‐α‐treated mice. In conclusion, while the anti‐TNF‐α treatment had neither immunosuppressive effects on the Th1/Th17 response in the CNS nor histoprotective properties in EAE, it enhanced the myelin‐specific T cell response in the immune periphery. |
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Keywords: | EAE/MS inflammation monocytes/macrophages neuroimmunology T cells |
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