Augmented production of chemokines by the interaction of type II collagen–reactive T cells with rheumatoid synovial fibroblasts

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Abstract
Objective To determine the impact of type II collagen (CII)–reactive T cells on the production of chemokines in the joints of patients with rheumatoid arthritis (RA). Methods T cell proliferative responses to bovine CII were assayed in synovial fluid (SF) mononuclear cells and peripheral blood mononuclear cells. CII‐stimulated T cells were cocultured with fibroblast‐like synoviocytes (FLS). The expression of interleukin‐8 (IL‐8), monocyte chemoattractant protein 1 (MCP‐1), and macrophage inflammatory protein 1α (MIP‐1α) in the sera, SF, and supernatant of the CII‐stimulated T cells and FLS coculture was measured by enzyme‐linked immunosorbent assays. Results The levels of IL‐8, MCP‐1, and MIP‐1α in SF were significantly higher than those in paired sera of RA patients. IL‐8, MCP‐1, and MIP‐1α levels in SF were strongly correlated with T cell responses to CII. When FLS were cocultured with CII‐stimulated T cells, the production of IL‐8, MCP‐1, and MIP‐1α was significantly increased. This increase correlated well with the T cell proliferative response to CII. Chemokine production by coculture of CII‐stimulated T cells and FLS was mediated mainly by direct cell–cell contact through CD40 ligand–CD40 engagement. Conclusion Our data indicate that the presence of CII‐reactive T cells in RA joints can increase the production of chemokines such as IL‐8, MCP‐1, and MIP‐1α through interaction with FLS. This chemokine production is mediated by cell–cell contact, including CD40 ligand–CD40 engagement. These results suggest that CII‐reactive T cells play a crucial role in the amplification and perpetuation of the inflammatory process in the rheumatoid synovium.