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Arthritis Res Ther. 2008;10(4):210. doi: 10.1186/ar2446. Epub 2008 Jul 24.

High avidity autoreactive T cells with a low signalling capacity through the T-cell receptor: central to rheumatoid arthritis pathogenesis?

Author information

1
Diamantina Institute for Cancer, Immunology and Metabolic Medicine, University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland 4102, Australia. r.thomas1@uq.edu.au

Abstract

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.

PMID:
18710589
PMCID:
PMC2575618
DOI:
10.1186/ar2446
[Indexed for MEDLINE]
Free PMC Article

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