EVIDENCE FOR THE ROLE OF AN ALTERED REDOX STATE IN HYPORESPONSIVENESSOF SYNOVIAL T-CELLS IN RHEUMATOID-ARTHRITIS

In rheumatoid arthritis (RA), T cells isolated from the synovial fluid (SF) show impaired responses to mitogenic stimulation compared with T cells from the peripheral blood (PB), Here it is reported that hypore sponsiveness of SF T cells correlated with a significant decrease in t he levels of the intracellular redox-regulating agent glutathione (GSH ). GSH was decreased in both CD4(+) (p = 0.0022) and CD8(+) (p = 0.001 0) SF T cell subsets compared with PB CD4(+) and CD8(+) T cells in RA patients. Levels of thioredoxin (TRX), another key redox mediator, pre viously found to be secreted under conditions of oxidative stress, wer e found to be significantly increased in SF compared with plasma sampl es of RA patients (p = 0.005), Increased levels of TRX in the SF of in flamed joints was found to be associated with RA when compared with Et her arthritides (p = 0.007), Restoration of GSH levels in SF T cells w ith N-acetyl-L-cysteine (NAG), enhanced mitogenic induced proliferativ e responses and IL-2 production. Collectively, these data impute an im portant role to an altered redox state in the hyporesponsiveness of jo int T cells in patients with RA.