Suppression of Autoimmune Neuritis in IFN-γ Receptor-Deficient Mice |
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Authors: | Yu Zhu Hans-Gustaf Ljunggren Eilhard Mix Hu-Lun Li Peter van der Meide Adlan M Elhassan Bengt Winblad Jie Zhu |
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Institution: | a Division of Geriatric Medicine, Department of Clinical Neuroscience, Department of Medicine, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden;b Department of Clinical Neuroscience, Center for Infectious Medicine, Department of Medicine, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden;e Department of Clinical Neuroscience, Department of Medicine, Department of Orthopedic Surgery, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden;c Department of Neurology, University of Rostock, Rostock, Germany;d Department of Cytokine Research, Central Laboratory Animal Institute (CLAI), University of Utrecht, Utrecht, The Netherlands |
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Abstract: | Experimental autoimmune neuritis (EAN) is an animal model of the human disease Guillain–Barré syndrome. In this autoimmune inflammatory disease, CD4+ T cells mediate demyelination in the peripheral nervous system (PNS). Infiltrating macrophages and T cells as well as cytokines like interferon (IFN)-γ are intimately involved in causing pathogenic effects. To investigate the role of IFN-γ in cell-mediated EAN, IFN-γ receptor-deficient mutant (IFN-γR−/−) C57BL/6 mice and corresponding wild-type mice were immunized with P0 peptide 180–199, a purified component of peripheral nerve myelin, and Freund's complete adjuvant. IFN-γR−/− mice exhibited later onset of clinical disease. The disease was also less severe than in wild-type mice. Fewer IL-12-producing but more IL-4-producing cells were found in sciatic nerve sections from IFN-γR−/− mice than from wild-type mice on day 24 postimmunization, i.e., at the peak of clinical EAN. At the same time, IFN-γR−/− mice had less infiltration of inflammatory cells, including macrophages, CD4+ T cells, and monocytes, into sciatic nerve tissue and less demyelination. However, numbers of IFN-γ-secreting cells from the spleen were significantly augmented in the IFN-γR−/− mice, reflecting a failure of negative feedback circuits. The IFN-γR deficiency did not affect the production of anti-P0 peptide 180–199-specific antibodies. These results indicate that IFN-γ contributes to a susceptibility for EAN in C57BL/6 mice by promoting a Th1 cell-mediated immune response and suppressing a Th2 response. |
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Keywords: | experimental autoimmune neuritis IFN-γ receptor-deficient mice Guillain– Barré syndrome Th1/Th2 cytokine |
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