Synovial Autoreactive T Cells in Rheumatoid Arthritis Resist IDO-Mediated Inhibition

摘要: A hallmark of T cell-mediated autoimmunity is the persistence autoreactive cells. However, it remains to elucidate manner in which synovial cells are sustained patients with rheumatoid arthritis (RA). We found that dendritic (DC) and tissues from joints RA expressed higher levels IDO than DC healthy donors. Interestingly, derived joint fluid (SF) proliferated response either autologous or allogeneic IDO-positive DC, an outcome was not affected by addition inhibitor 1-methyl-d-tryptophan (1-MT). In contrast, 1-MT culture stimulated significantly enhanced proliferation peripheral blood donors patients. Furthermore, we functionally active tryptophanyl-tRNA-synthetase (TTS) elevated SF patients, leading storage tryptophan subsequent resistance IDO-mediated deprivation tryptophan. The enhancement TTS expression blocked mAb IFN-γ TNF-α. These results suggest represents a mechanism vivo Specifically, blocking up-regulation presents avenue for development novel therapeutic approach treatment RA.