Email updates

Keep up to date with the latest news and content from Arthritis Research & Therapy and BioMed Central.

Review

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

Ranjeny Thomas1*, Malcolm Turner1 and Andrew P Cope2

Author Affiliations

1 Diamantina Institute for Cancer, Immunology and Metabolic Medicine, University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland, 4102, Australia

2 The Kennedy Institute of Rheumatology, Faculty of Medicine, Imperial College, 1 Aspenlea Road, Hammersmith, London W6 8LH, UK

For all author emails, please log on.

Arthritis Research & Therapy 2008, 10:210  doi:10.1186/ar2446

Published: 24 July 2008

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-κB 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.