title: Inducing experimental arthritis and breaking self-tolerance to joint-specific antigens with trackable, ovalbumin-specific T cells.
abstract: The importance of T cell Ag specificity and Th1 vs Th2 phenotype in synovial inflammation remains controversial. Using OVA-specific TCR transgenic T cells from DO11.10 mice, we demonstrate that mice receiving Th1, but not Th2, cells display a transient arthritis following immunization that is characterized by synovial hyperplasia, cellular infiltration, and cartilage erosion. OVA-specific T cells also accumulated in inflamed joints, suggesting that they could exert their inflammatory effect locally in the joint or in the draining lymph node. Importantly, this pathology was accompanied by a breakdown in self-tolerance, as evidenced by the induction of collagen-specific T and B cell responses. This model directly demonstrates a pivotal role for Th1 cells of an irrelevant specificity in the development of inflammatory arthritis. Furthermore, the ability to track these cells in vivo will make feasible studies revealing the dynamic role of T cells in arthritis.
authors.affiliation: Division of Immunology, Infection, and Inflammation, University of Glasgow, Western Infirmary, Glasgow, Scotland G11 6NT, UK.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Maffia
authors.forename: James M
authors.initials: JM
authors.lastname: Brewer
authors.forename: J Alastair
authors.initials: JA
authors.lastname: Gracie
authors.forename: Angela
authors.initials: A
authors.lastname: Ianaro
authors.forename: Bernard P
authors.initials: BP
authors.lastname: Leung
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Mitchell
authors.forename: Karen M
authors.initials: KM
authors.lastname: Smith
authors.forename: Iain B
authors.initials: IB
authors.lastname: McInnes
authors.forename: Paul
authors.initials: P
authors.lastname: Garside
mesh_terms: D000818:Animals; D000917:Antibody Formation; D001169:Arthritis, Experimental / Q000209:etiology / Q000276:immunology*; D002478:Cells, Cultured; D024043:Collagen Type II / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D007108:Immune Tolerance; D007150:Immunohistochemistry; D016130:Immunophenotyping; D007596:Joints / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D024043:Collagen Type II; D016207:Cytokines; D011948:Receptors, Antigen, T-Cell; D010047:Ovalbumin