title: Augmented production of chemokines by the interaction of type II collagen-reactive T cells with rheumatoid synovial fibroblasts.
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 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.
authors.affiliation: Catholic Research Institutes of Medical Sciences, Catholic University of Korea, Seoul, Korea.
authors.forename: Do-June
authors.initials: DJ
authors.lastname: Min
authors.forename: Mi-La
authors.initials: ML
authors.lastname: Cho
authors.forename: Sang-Heon
authors.initials: SH
authors.lastname: Lee
authors.forename: So-Youn
authors.initials: SY
authors.lastname: Min
authors.forename: Wan-Uk
authors.initials: WU
authors.lastname: Kim
authors.forename: Jun-Ki
authors.initials: JK
authors.lastname: Min
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Park
authors.forename: Chul-Soo
authors.initials: CS
authors.lastname: Cho
authors.forename: Ho-Youn
authors.initials: HY
authors.lastname: Kim
mesh_terms: 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
chemical_list: 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