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Báo cáo y học: " High avidity autoreactive T cells with a low signalling capacity through the T-cell receptor: central to rheumatoid arthritis pathogenesis"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học General Psychiatry cung cấp cho các bạn kiến thức về ngành y đề tài: High avidity autoreactive T cells with a low signalling capacity through the T-cell receptor: central to rheumatoid arthritis pathogenesis? | Available online http arthritis-research.eom content 10 4 210 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 1 Diamantina 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 Corresponding author Ranjeny Thomas r.thomas1@uq.edu.au Published 24 July 2008 This article is online at http arthritis-research.com content 10 4 210 2008 BioMed Central Ltd Arthritis Research Therapy 2008 10 210 doi 10.1186 ar2446 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-KB 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. Introduction In 1996 Thomas and Lipsky 1 proposed a model for rheumatoid arthritis RA pathogenesis in which endogenous self-antigens were presented by activated peripheral dendritic cells DCs to autoreactive T cells that had escaped thymic selection. Synovial DCs were shown to be activated probably as a consequence of proinflammatory signals derived from the RA joint environment including cytokines and T-cell derived CD40 ligand 1 2 . The model stemmed from observations that autologous peripheral blood T cells proliferated strongly in vitro in response to .