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 1 alpha (mip-1 alpha) 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-1 alpha in sf were significantly higher than those in paired sera of ra patients. il-8, mcp-1, and mip-1 alpha 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-1 alpha 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-1 alpha 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.