Abstract
Recent clinical trials have established B cell depletion by the anti-CD20 chimeric antibody Rituximab as a beneficial therapy for patients with relapsing-remitting multiple sclerosis (MS). The impact of Rituximab on T cell responses remains largely unexplored. In the experimental autoimmune encephalomyelitis (EAE) model of MS in mice that express human CD20, Rituximab administration rapidly depleted peripheral B cells and strongly reduced EAE severity. B cell depletion was also associated with diminished Delayed Type Hypersensitivity (DTH) and a reduction in T cell proliferation and IL-17 production during recall immune response experiments. While Rituximab is not considered a broad immunosuppressant, our results indicate a role for B cells as a therapeutic cellular target in regulating encephalitogenic T cell responses in specific tissues.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Monoclonal / therapeutic use
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Antibodies, Monoclonal, Murine-Derived / therapeutic use*
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Autoimmunity / drug effects*
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Autoimmunity / immunology
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Down-Regulation / drug effects
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Down-Regulation / immunology
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Drug Evaluation, Preclinical
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Encephalomyelitis, Autoimmune, Experimental / complications
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Encephalomyelitis, Autoimmune, Experimental / drug therapy*
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Encephalomyelitis, Autoimmune, Experimental / immunology*
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Encephalomyelitis, Autoimmune, Experimental / pathology
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Immunity, Cellular / drug effects*
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Immunologic Factors / therapeutic use
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Multiple Sclerosis, Relapsing-Remitting / complications
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Multiple Sclerosis, Relapsing-Remitting / drug therapy
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Multiple Sclerosis, Relapsing-Remitting / immunology
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Multiple Sclerosis, Relapsing-Remitting / pathology
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Organ Specificity / drug effects
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Organ Specificity / immunology
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Rituximab
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T-Lymphocytes / drug effects
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T-Lymphocytes / immunology*
Substances
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Antibodies, Monoclonal
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Antibodies, Monoclonal, Murine-Derived
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Immunologic Factors
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Rituximab