Are T cells in rheumatoid synovium aggressors or bystanders?

T cells have been directly associated with rheumatoid arthritis (RA) because they represent the largest cell population infiltrating the synovium. Their direct contribution to disease and joint destruction has been more difficult to demonstrate. Locally, they interact with other blood-derived and resident cells. Some T cells may contribute to disease through the secretion of cytokines. Indeed, interleukin-17, a T-cell-specific cytokine, is produced by RA synovium and acts as a bone and cartilage destructive factor. In addition, it increases the production of proinflammatory cytokines by monocytes and further enhances their effects on matrix destruction. Once considered bystanders in RA, T cells can now be classified as aggressors through their direct and indirect contribution to destruction. In particular, a subset of Th1 T cells can aggravate the proinflammatory and destructive pattern associated with monocyte activation. Manipulation of this subset may control the destructive pattern. Such a result can be achieved when a switch can be induced from a destructive pattern to a protective one leading to repair.