Rituximab therapy reduces organ-specific T cell responses and ameliorates experimental autoimmune encephalomyelitis

• Published in: PloS one 2011-02, Vol.6 (2), p.e17103
• Main Authors: Monson, Nancy L, Cravens, Petra, Hussain, Rehana, Harp, Christopher T, Cummings, Matthew, de Pilar Martin, Maria, Ben, Li-Hong, Do, Julie, Lyons, Jeri-Anne, Lovette-Racke, Amy, Cross, Anne H, Racke, Michael K, Stüve, Olaf, Shlomchik, Mark, Eagar, Todd N
• Format: Article
• Language: English
• Subjects: Animal tissues; Animals; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Murine-Derived - therapeutic use; Autoimmunity - drug effects; Autoimmunity - immunology; B cells; Biology; CD20 antigen; Cell growth; Cell proliferation; Clinical trials; Cytokines; Dendritic cells; Depletion; Development and progression; Down-Regulation - drug effects; Down-Regulation - immunology; Drug Evaluation, Preclinical; Encephalomyelitis; Encephalomyelitis, Autoimmune, Experimental - complications; Encephalomyelitis, Autoimmune, Experimental - drug therapy; Encephalomyelitis, Autoimmune, Experimental - immunology; Encephalomyelitis, Autoimmune, Experimental - pathology; Experimental allergic encephalomyelitis; Glycoproteins; Hypersensitivity; Hypersensitivity (delayed); Immune response; Immune system; Immunity, Cellular - drug effects; Immunologic Factors - therapeutic use; Immunology; Immunosuppressive agents; Immunotherapy; Interleukin 17; Lymphocytes; Lymphocytes B; Lymphocytes T; Medical research; Mice; Mice, Inbred C57BL; Mice, Transgenic; Monoclonal antibodies; Multiple sclerosis; Multiple Sclerosis, Relapsing-Remitting - complications; Multiple Sclerosis, Relapsing-Remitting - drug therapy; Multiple Sclerosis, Relapsing-Remitting - immunology; Multiple Sclerosis, Relapsing-Remitting - pathology; Nervous system; Neurology; Organ Specificity - drug effects; Organ Specificity - immunology; Rituximab; T cell receptors; T cells; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; Therapy
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0017103

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.