Increased intraarticular interleukin-7 in rheumatoid arthritis patients stimulates cell contact-dependent activation of CD4(+) T cells and macrophages

OBJECTIVE: To determine the level of intraarticular expression of interleukin-7 (IL-7) in patients with rheumatoid arthritis (RA) and to investigate the mechanisms by which IL-7 facilitates activation of CD4(+) T cells and monocyte/macrophages in RA. METHODS: IL-7 levels were measured in synovial fluid obtained from patients with RA and patients with osteoarthritis (OA). Immunohistologic analysis was used to assess the expression of IL-7 in synovial tissue from patients with RA. Proliferation and activation markers were determined in order to measure the effect of IL-7 on mononuclear cells, isolated CD4(+) T cells, and monocyte/macrophages from the peripheral blood and synovial fluid. Cocultures of CD4(+) T cells and monocytic cells in the absence or presence of a semipermeable membrane were performed to assess the extent to which IL-7 induces its effects, either contact dependently or via soluble mediators. RESULTS: IL-7 levels were increased in synovial fluid from patients with RA compared with the levels in synovial fluid from patients with OA. Macrophages, fibroblasts, and endothelial cells in the joint lining tissue expressed abundant IL-7. In vitro, synovial fluid CD4(+) T cells and macrophages were hyperresponsive to IL-7 when compared with peripheral blood cells. Furthermore, IL-7 enhanced cell contact-dependent activation of CD4(+) T cells and monocyte/macrophages. CONCLUSION: The abundant intraarticular expression of IL-7 and the stimulation by IL-7 of contact-dependent activation of CD4(+) T cells and monocytic cells indicate that this cytokine plays an important proinflammatory role in RA synovitis. Further identification of IL-7-induced pathways may improve understanding of the important interactive role of CD4(+) T cells and monocytic cells in RA.