No area in rheumatology research has undergone such extensive evolution over the last 10 years as the pathophysiology of rheumatoid arthritis (RA). Dramatic new therapeutic approaches have been developed, rapidly following advances in knowledge about cellular events in the rheumatoid synovium. However, the widely publicized promise of these new therapeutic agents has often been dampened by the initial results of clinical trials, which appeared less exciting than anticipated. Arthritis & Rheumatism has published 5 review articles about the pathophysiology and treatment of RA over the last 14 months (1-5), the last one, in this issue, on T cells. The objective of this editorial is to provide some perspective and commentary on this area of basic and clinical research.

The current concept is that inflammation and tissue destruction in the rheumatoid synovium result from complex cell-cell interactions. These events are thought to be initiated by an interaction between antigen-presenting cells (APC) and CD4+ T cells; APC display complexes of class I1 major histocompatibility complex (MHC) molecules and peptide antigen (s) that bind to specific receptors on the T cells. Macrophage activation ensues, with secretion of proinflammatory cytokines such as interleukin-1 (IL-1) and tumor necrosis factor a (TNFa). These cytokines stimulate synovial fibroblasts and chondrocytes in the nearby articular cartilage to secrete enzymes that degrade proteoglycans and collagen, leading to tissue destruction. However, this simplified scheme is based on many tenuous assumptions that are continuously being challenged.