title: Arthritogenic T cells drive the recovery of autoantibody-producing B cell homeostasis and the adoptive transfer of arthritis in SCID mice.
abstract: T cells orchestrate joint inflammation in rheumatoid arthritis (RA), but B cells/B cell-derived factors are also involved in disease pathogenesis. The goal of this study was to understand the role of antigen-specific T and B cells in the pathological events of arthritis, which is impossible to study in humans due to the small number of antigen-specific cells. To determine the significance of antigen-specific lymphocytes and antibodies in the development of an autoimmune mouse model of RA, we generated TCR transgenic (TCR-Tg) mice specific for the dominant arthritogenic epitope of cartilage proteoglycan (PG) and performed a series of combined transfers of T cells, B cells and autoantibodies into BALB/c.Scid mice. The adoptive transfer of highly purified T cells from naive TCR-Tg, arthritic TCR-Tg or arthritic wild-type mice induced arthritis in SCID recipients, but the onset and severity of the disease were dependent on the sequential events of the T cell-supported reconstitution of PG-specific B cells and autoantibodies. The presence of activated PG-specific T cells was critical for disease induction, establishing a unique milieu for the selective homeostasis of autoantibody-producing B cells. In this permissive environment, anti-PG autoantibodies bound to cartilage and induced activation of the complement cascade, leading to irreversible cartilage destruction in affected joints. These findings may lead to a better understanding of the complex molecular and cellular mechanisms of RA.
authors.affiliation: Department of Molecular Medicine, Rush University Medical Center, Chicago, IL 60612, USA. kkistoth@bidmc.harvard.edu
authors.forename: Katalin
authors.initials: K
authors.lastname: Kis-Toth
authors.forename: Marianna
authors.initials: M
authors.lastname: Radacs
authors.forename: Katalin
authors.initials: K
authors.lastname: Olasz
authors.forename: Willem
authors.initials: W
authors.lastname: van Eden
authors.forename: Katalin
authors.initials: K
authors.lastname: Mikecz
authors.forename: Tibor T
authors.initials: TT
authors.lastname: Glant
mesh_terms: D019264:Adoptive Transfer; D053674:Aggrecans / Q000276:immunology; D000818:Animals; D000917:Antibody Formation; D001169:Arthritis, Experimental / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D006706:Homeostasis / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D053674:Aggrecans; D001323:Autoantibodies; D001324:Autoantigens