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Eur J Immunol. 1998 Sep;28(9):2661-71.

Interleukin-16, produced by synovial fibroblasts, mediates chemoattraction for CD4+ T lymphocytes in rheumatoid arthritis.

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Center of Experimental Rheumatology, Department of Rheumatology, University Hospital, Z├╝rich, Switzerland.


The massive infiltration of synovium with CD4+ T cells during the course of rheumatoid arthritis (RA) implies the expression of chemoattractant factors by resident synovial cells. Therefore, we analyzed the expression of IL-16, a potent chemoattractant for CD4+ T cells, to account for the accumulation of CD4+ T cells in RA. Indeed, IL-16 was found to be significantly elevated in synovial fluid (SF) from patients 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 hybridization (ISH) revealed IL-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, mainly adjacent to blood vessels. By a double-labeling technique, combining ISH for IL-16 mRNA and immunohistochemistry for CD68, synovial fibroblast-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 CD4+ cells into synovial tissue.

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