Studies of T-cell activation in chronic inflammation 英文参考文献.docVIP

Available online /content/4/S3/S197 Supplement Review Studies of T-cell activation in chronic inflammation Andrew P Cope The Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College, London, UK Correspondence: Andrew P Cope, The Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College, Arthritis Research Campaign Building, 1 Aspenlea Road, Hammersmith, London W6 8LH, UK. Tel: +44 (0)20 8383 4444; fax: +44 (0)20 8383 4499; e-mail: andrew.cope@ic.ac.uk Received: 3 January 2002 Accepted: 21 January 2002 Published: 9 May 2002 Arthritis Res 2002, 4 (suppl 3):S197-S211 ? 2002 BioMed Central Ltd (Print ISSN 1465-9905; Online ISSN 1465-9913) Chapter summary The strong association between specific alleles encoded within the MHC class II region and the development of rheumatoid arthritis (RA) has provided the best evidence to date that CD4+ T cells play a role in the pathogenesis of this chronic inflammatory disease. However, the unusual phenotype of synovial T cells, including their profound proliferative hyporesponsiveness to TCR ligation, has challenged the notion that T-cell effector responses are driven by cognate cartilage antigens in inflamed synovial joints. The hierarchy of T-cell dysfunction from peripheral blood to inflamed joint suggests that these defects are acquired through prolonged exposure to proinflammatory cytokines such as tumour necrosis factor (TNF)-α. Indeed, there are now compelling data to suggest that chronic cytokine activation may contribute substantially to the phenotype and effector function of synovial T cells. Studies reveal that chronic exposure of T cells to TNF uncouples TCR signal transduction pathways by impairing the assembly and stability of the TCR/CD3 complex at the cell surface. Despite this membrane-proximal effect, TNF selectively uncouples downstream signalling pathways, as is shown by the dramatic