title: Monoclonal antibody against T-cell receptor alphabeta induces self-tolerance in chronic experimental autoimmune encephalomyelitis.
abstract: The therapeutic effect of monoclonal antibody (H57-597 MoAb) against T-cell receptor (TCR) alphabeta has been investigated on MOG(35-55)-induced experimental autoimmune encephalomyelitis (EAE), as a model system for T-cell-mediated chronic inflammation in the central nervous system (CNS). Short-term administration of the anti-TCR alphabeta immediately after immunization protected the mice from EAE. Furthermore, anti-TCR alphabeta treatment on an established disease restored the self-tolerance which led to a complete remission of EAE and a dramatic reduction of inflammatory cells in the CNS, while treatment with control antibody (hamster IgG) was ineffective. The remission was durable and not associated with disappearance of autoreactive T cells as measured by persistence of MOG-reactive T-cell proliferation in vitro. However, MOG-reactive T cells from anti-TCR-treated animals produced significantly lower amounts of inflammatory TNF-alpha and IFN-gamma. In addition, while a transient deletion of CD4(+) and CD8(+) T cells was observed, a population of T cells expressing CD3, NK1.1 and CD69 (NKT cells) were expanding. By transfer of spleen cells from anti-TCR MoAb-treated animals, we could show that the tolerogenic capacity can be transferred to untreated recipients with EAE. The data indicate therapeutic effect of anti-TCR alphabeta MoAb (H57-597), which represents a promising approach in treatment of T-cell-mediated autoimmune diseases.
authors.affiliation: Department of Experimental Medical Science, Medical Inflammation Research, Lund University, Lund, Sweden. shahram.lavasani@cob.lu.se
authors.forename: S
authors.initials: S
authors.lastname: Lavasani
authors.forename: B
authors.initials: B
authors.lastname: Dzhambazov
authors.forename: M
authors.initials: M
authors.lastname: Andersson
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D000950:Antigens, Ly; D000954:Antigens, Surface / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002908:Chronic Disease; D004306:Dose-Response Relationship, Immunologic; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000628:therapy*; D005260:Female; D037181:Lectins, C-Type / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D055651:NK Cell Lectin-Like Receptor Subfamily B; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D017634:Self Tolerance; D013154:Spleen / Q000276:immunology; D000099192:CD69 Antigens
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000950:Antigens, Ly; D000954:Antigens, Surface; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D016693:Receptors, Antigen, T-Cell, alpha-beta; D000099192:CD69 Antigens; C527211:Klrb1c protein, mouse