title: Rituximab therapy reduces organ-specific T cell responses and ameliorates experimental autoimmune encephalomyelitis.
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.
authors.affiliation: Department of Neurology, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Monson
authors.forename: Petra
authors.initials: P
authors.lastname: Cravens
authors.forename: Rehana
authors.initials: R
authors.lastname: Hussain
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Harp
authors.forename: Matthew
authors.initials: M
authors.lastname: Cummings
authors.forename: Maria
authors.initials: M
authors.lastname: de Pilar Martin
authors.forename: Li-Hong
authors.initials: LH
authors.lastname: Ben
authors.forename: Julie
authors.initials: J
authors.lastname: Do
authors.forename: Jeri-Anne
authors.initials: JA
authors.lastname: Lyons
authors.forename: Amy
authors.initials: A
authors.lastname: Lovette-Racke
authors.forename: Anne H
authors.initials: AH
authors.lastname: Cross
authors.forename: Michael K
authors.initials: MK
authors.lastname: Racke
authors.forename: Olaf
authors.initials: O
authors.lastname: Stüve
authors.forename: Mark
authors.initials: M
authors.lastname: Shlomchik
authors.forename: Todd N
authors.initials: TN
authors.lastname: Eagar
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D015551:Autoimmunity / Q000187:drug effects* / Q000276:immunology; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D004353:Drug Evaluation, Preclinical; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000150:complications / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D007111:Immunity, Cellular / Q000187:drug effects*; D007155:Immunologic Factors / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000150:complications / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D009928:Organ Specificity / Q000187:drug effects / Q000276:immunology; D000069283:Rituximab; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D007155:Immunologic Factors; D000069283:Rituximab