Augmented production of chemokines by the interaction of type II collagen–reactive T cells with rheumatoid synovial fibroblasts
Do-June Min
Catholic Research Institutes of Medical Sciences, Catholic University of Korea, Seoul, Korea
Search for more papers by this authorMi-La Cho
Catholic Research Institutes of Medical Sciences, Catholic University of Korea, Seoul, Korea
Search for more papers by this authorSang-Heon Lee
Catholic Research Institutes of Medical Sciences, Catholic University of Korea, Seoul, Korea
Search for more papers by this authorSo-Youn Min
Catholic Research Institutes of Medical Sciences, Catholic University of Korea, Seoul, Korea
Search for more papers by this authorWan-Uk Kim
Catholic Research Institutes of Medical Sciences, Catholic University of Korea, Seoul, Korea
Search for more papers by this authorJun-Ki Min
Catholic Research Institutes of Medical Sciences, Catholic University of Korea, Seoul, Korea
Search for more papers by this authorSung-Hwan Park
Catholic Research Institutes of Medical Sciences, Catholic University of Korea, Seoul, Korea
Search for more papers by this authorChul-Soo Cho
Catholic Research Institutes of Medical Sciences, Catholic University of Korea, Seoul, Korea
Search for more papers by this authorCorresponding Author
Ho-Youn Kim
Catholic Research Institutes of Medical Sciences, Catholic University of Korea, Seoul, Korea
The Center for Rheumatic Diseases, Kang-Nam St. Mary's Hospital, Division of Rheumatology, Department of Internal Medicine, School of Medicine, Catholic University of Korea, No. 505 Banpo-Dong, Seocho-Ku, Seoul 137-040, KoreaSearch for more papers by this authorDo-June Min
Catholic Research Institutes of Medical Sciences, Catholic University of Korea, Seoul, Korea
Search for more papers by this authorMi-La Cho
Catholic Research Institutes of Medical Sciences, Catholic University of Korea, Seoul, Korea
Search for more papers by this authorSang-Heon Lee
Catholic Research Institutes of Medical Sciences, Catholic University of Korea, Seoul, Korea
Search for more papers by this authorSo-Youn Min
Catholic Research Institutes of Medical Sciences, Catholic University of Korea, Seoul, Korea
Search for more papers by this authorWan-Uk Kim
Catholic Research Institutes of Medical Sciences, Catholic University of Korea, Seoul, Korea
Search for more papers by this authorJun-Ki Min
Catholic Research Institutes of Medical Sciences, Catholic University of Korea, Seoul, Korea
Search for more papers by this authorSung-Hwan Park
Catholic Research Institutes of Medical Sciences, Catholic University of Korea, Seoul, Korea
Search for more papers by this authorChul-Soo Cho
Catholic Research Institutes of Medical Sciences, Catholic University of Korea, Seoul, Korea
Search for more papers by this authorCorresponding Author
Ho-Youn Kim
Catholic Research Institutes of Medical Sciences, Catholic University of Korea, Seoul, Korea
The Center for Rheumatic Diseases, Kang-Nam St. Mary's Hospital, Division of Rheumatology, Department of Internal Medicine, School of Medicine, Catholic University of Korea, No. 505 Banpo-Dong, Seocho-Ku, Seoul 137-040, KoreaSearch for more papers by this authorAbstract
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.
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