INTERLEUKIN-16, PRODUCED BY SYNOVIAL FIBROBLASTS, MEDIATES CHEMOATTRACTION FOR CD4(-LYMPHOCYTES IN RHEUMATOID-ARTHRITIS() T)

The massive infiltration of synovium with CD4(+) T cells during the co urse of rheumatoid arthritis (RA) implies the expression of chemoattra ctant factors by resident synovial cells. Therefore, we analyzed the e xpression of IL-16, a potent chemoattractant for CD4(+) T cells, to ac count for the accumulation of CD4(+) T cells in RA. Indeed, IL-16 was found to be significantly elevated in synovial fluid (SF) from patient s with RA as compared to non-RA arthritis (p < 0.001), osteoarthritis (p < 0.001) and controls (p < 0.001). Chemotaxis studies showed IL-16 to contribute to the strong chemotactic activities of RA-SF. In situ h ybridization (ISH) revealed 11-16 mRNA-expressing cells located within the lining layer of rheumatoid synovial tissue. In the sublining area , only scattered IL-16 transcript-positive cells could be detected, ma inly adjacent to blood vessels. By a double-labeling technique, combin ing ISH for IL-16 mRNA and immunohistochemistry for CD68, synovial fib roblast-like, CD68-negative cells were identified as a major source of IL-16 mRNA within RA synovium. This study demonstrates that synovial fibroblasts produce IL-16 in RA and thus mediate chemoattraction of CD 4(+) cells into synovial tissue.