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

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

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

author email corresponding author email

Arthritis Research & Therapy 2008, 10:210doi: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.