Figure 1

Pathways by which T cell interactions can contribute to synovial inflammation. T cells activated by cytokine combinations, by contact between extracellular matrix and endothelium and potentially by autoantigen, can activate the production of cytokines, MMPs and prostaglandins (PGs) by macrophages and FLS, creating potential positive feedback loops, and leading in turn to articular damage. Contact interactions might be variably mediated through adhesion molecules or membrane cytokines. The parallel secretion of pro-inflammatory and anti-inflammatory cytokines and cytokine receptors further modulate responses. The production by FLS of cytokines, such as IL-7, IL-15 and IL-18, that activate T cells is likely, but because few studies have yet directly addressed this issue, these pathways have been omitted. Interactions between synovial T and B lymphocytes are beyond the scope of this review.