Immunization with glucose-6-phosphate isomerase induces T cell-dependent peripheral polyarthritis in genetically unaltered mice.
Rheumatoid arthritis is a chronic inflammatory disease primarily affecting the joints. The search for arthritogenic autoantigens that trigger autoimmune responses in rheumatoid arthritis has largely focused on cartilage- or joint-specific Ags. In this study, we show that immunization with the ubiquitously expressed glycolytic enzyme glucose-6-phosphate isomerase (G6PI) induces severe peripheral symmetric polyarthritis in normal mice. In genetically unaltered mice, T cells are indispensable for both the induction and the effector phase of G6PI-induced arthritis. Arthritis is cured by depletion of CD4(+) cells. In contrast, Abs and FcgammaR(+) effector cells are necessary but not sufficient for G6PI-induced arthritis in genetically unaltered mice. Thus, the complex pathogenesis of G6PI-induced arthritis in normal mice differs strongly from the spontaneously occurring arthritis in the transgenic K/B x N model where Abs against G6PI alone suffice to induce the disease. G6PI-induced arthritis demonstrates for the first time the induction of organ-specific disease by systemic autoimmunity in genetically unaltered mice. Both the induction and effector phase of arthritis induced by a systemic autoimmune response can be dissected and preventive and therapeutic strategies evaluated in this model.
Schubert
David
D
Deutsches Rheumaforschungszentrum Berlin, Berlin, Germany.
Maier
Bert
B
Morawietz
Lars
L
Krenn
Veit
V
Kamradt
Thomas
T
D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D001169:Arthritis, Experimental / Q000201:enzymology* / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D001323:Autoantibodies / Q000096:biosynthesis / Q000502:physiology; D001324:Autoantigens / Q000008:administration & dosage / Q000276:immunology; D015704:CD4 Antigens / Q000096:biosynthesis / Q000276:immunology; D020022:Genetic Predisposition to Disease; D005956:Glucose-6-Phosphate Isomerase / Q000008:administration & dosage* / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics; D007113:Immunity, Innate / Q000235:genetics; D007114:Immunization / Q000379:methods; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008212:Lymphocyte Depletion; D051379:Mice; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D019138:Antibodies, Blocking; D001323:Autoantibodies; D001324:Autoantigens; D015704:CD4 Antigens; D014409:Tumor Necrosis Factor-alpha; D005956:Glucose-6-Phosphate Isomerase