| First Author | Kobayashi M | Year | 2004 |
| Journal | Arthritis Rheum | Volume | 50 |
| Issue | 12 | Pages | 3974-84 |
| PubMed ID | 15593201 | Mgi Jnum | J:106272 |
| Mgi Id | MGI:3617956 | Doi | 10.1002/art.20679 |
| Citation | Kobayashi M, et al. (2004) Development of autoimmune arthritis with aging via bystander T cell activation in the mouse model of Sjogren's syndrome. Arthritis Rheum 50(12):3974-84 |
| abstractText | OBJECTIVE: A wide spectrum of extraglandular manifestations may occur in patients with Sjogren's syndrome (SS), but the mechanisms responsible for in vivo progression are still obscure. We undertook this study to evaluate the age-related changes during the development of extraglandular autoimmune lesions, including arthritis, in the murine model of primary SS, and to evaluate the possible relationship between age-related disturbance of activation-induced cell death and the in vivo kinetics against autoantigens. METHODS: A total of 126 NFS/sld mice were investigated at ages 2, 4, 6, 10, 12, 18, 20, and 24 months. Cytokine production was tested using culture supernatants from anti-CD3 monoclonal antibody-stimulated T cells. Anti-single-stranded DNA (anti-ssDNA) antibodies, Ig isotypes (IgG1, IgG2a), rheumatoid factor (RF), and anti-type II collagen (anti-CII) antibodies were detected by enzyme-linked immunosorbent assay. Proliferative T cell responses against each of 3 recombinant alpha-fodrin proteins and against CII were analyzed. RESULTS: Autoimmune arthritis developed in SS model mice until age 24 months. Significant elevations in serum levels of RF, anti-ssDNA antibodies, and anti-CII antibodies were found in aging SS model mice. A high titer of serum autoantibodies against alpha-fodrin fragments (containing different epitopes that were originally identified in primary SS model mice) was frequently detected in young and aged SS model mice. Moreover, we found that alpha-fodrin autoantigen induced Th1 immune responses and accelerated disturbance of Fas-mediated T cell apoptosis in aged SS model mice. CONCLUSION: These results indicate that age-related disturbance of activation-induced cell death via bystander T cell activation may play a crucial role in the development of autoimmune arthritis in a murine model of SS. |
