title: Organ-specific disease provoked by systemic autoimmunity.
abstract: Rheumatoid arthritis (RA) is a chronic joint disease characterized by leukocyte invasion and synoviocyte activation followed by cartilage and bone destruction. Its etiology and pathogenesis are poorly understood. We describe a spontaneous mouse model of this syndrome, generated fortuitously by crossing a T cell receptor (TCR) transgenic line with the NOD strain. All offspring develop a joint disease highly reminiscent of RA in man. The trigger for the murine disorder is chance recognition of a NOD-derived major histocompatibility complex (MHC) class II molecule by the transgenic TCR; progression to arthritis involves CD4+ T, B, and probably myeloid cells. Thus, a joint-specific disease need not arise from response to a joint-specific antigen but can be precipitated by a breakdown in general mechanisms of self-tolerance resulting in systemic self-reactivity. We suggest that human RA develops by an analogous mechanism.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire (CNRS/INSERM/ULP), Illkirch, France.
authors.forename: V
authors.initials: V
authors.lastname: Kouskoff
authors.forename: A S
authors.initials: AS
authors.lastname: Korganow
authors.forename: V
authors.initials: V
authors.lastname: Duchatelle
authors.forename: C
authors.initials: C
authors.lastname: Degott
authors.forename: C
authors.initials: C
authors.lastname: Benoist
authors.forename: D
authors.initials: D
authors.lastname: Mathis
mesh_terms: D000483:Alleles; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology / Q000503:physiopathology*; D001327:Autoimmune Diseases / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology; D002451:Cell Compartmentation / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D019076:Transgenes / Q000276:immunology
chemical_list: D000949:Histocompatibility Antigens Class II; D011948:Receptors, Antigen, T-Cell