High avidity autoreactive T cells with a low signalling capacity through the T-cell receptor: central to rheumatoid arthritis pathogenesis?
Self-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.
Thomas
Ranjeny
R
Diamantina Institute for Cancer, Immunology and Metabolic Medicine, University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland 4102, Australia. r.thomas1@uq.edu.au
Turner
Malcolm
M
Cope
Andrew P
AP
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000209:etiology / Q000503:physiopathology*; D004195:Disease Models, Animal; D051379:Mice; D016328:NF-kappa B / Q000502:physiology; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D016328:NF-kappa B; D011948:Receptors, Antigen, T-Cell; D014409:Tumor Necrosis Factor-alpha