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


CONCLUSIONS
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.
Min
Do-June
DJ
Catholic Research Institutes of Medical Sciences, Catholic University of Korea, Seoul, Korea.
Cho
Mi-La
ML
Lee
Sang-Heon
SH
Min
So-Youn
SY
Kim
Wan-Uk
WU
Min
Jun-Ki
JK
Park
Sung-Hwan
SH
Cho
Chul-Soo
CS
Kim
Ho-Youn
HY
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D019013:CD40 Antigens / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000097:blood; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018925:Chemokines / Q000097:blood*; D018920:Coculture Techniques; D024043:Collagen Type II / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D016209:Interleukin-8 / Q000097:blood; D019402:Macrophage Inflammatory Proteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D013582:Synovial Fluid / Q000276:immunology / Q000378:metabolism; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018925:Chemokines; D024043:Collagen Type II; D016209:Interleukin-8; D019402:Macrophage Inflammatory Proteins