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lüll High avidity autoreactive T cells with a low signalling capacity through the T-cell receptor: central to rheumatoid arthritis pathogenesis?Thomas R; Turner M; Cope APArthritis Res Ther 2008[]; 10 (4): 210Self-reactive T cells with low signalling capacity through the T-cell receptor were recently observed in the SKG mouse model of rheumatoid arthritis (RA) and have been linked to a spontaneous mutation in the ZAP-70 signal transduction molecule. Here we hypothesize that similar mechanisms also drive RA, associated with an abnormal innate and adaptive immune response driven by nuclear factor-kappaB activation and tumour necrosis factor secretion. Similar to the essential role played by pathogens in SKG mice, we propose that HLA-associated immunity to chronic viral infection is a key factor in the immune dysregulation and joint inflammation that characterize RA.|Animals[MESH]|Arthritis, Rheumatoid/etiology/*physiopathology[MESH]|Disease Models, Animal[MESH]|Mice[MESH]|NF-kappa B/physiology[MESH]|Receptors, Antigen, T-Cell/*physiology[MESH]|Signal Transduction/physiology[MESH]|T-Lymphocytes/*physiology[MESH]|Tumor Necrosis Factor-alpha/physiology[MESH] |