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

PLoS One. 2011 Feb 16;6(2):e17103. doi: 10.1371/journal.pone.0017103.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use*
  • Autoimmunity / drug effects*
  • Autoimmunity / immunology
  • Down-Regulation / drug effects
  • Down-Regulation / immunology
  • Drug Evaluation, Preclinical
  • Encephalomyelitis, Autoimmune, Experimental / complications
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy*
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Immunity, Cellular / drug effects*
  • Immunologic Factors / therapeutic use
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Multiple Sclerosis, Relapsing-Remitting / complications
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy
  • Multiple Sclerosis, Relapsing-Remitting / immunology
  • Multiple Sclerosis, Relapsing-Remitting / pathology
  • Organ Specificity / drug effects
  • Organ Specificity / immunology
  • Rituximab
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Immunologic Factors
  • Rituximab