PMID- 10529123 OWN - NLM STAT- MEDLINE DCOM- 19991118 LR - 20171116 IS - 0315-162X (Print) IS - 0315-162X (Linking) VI - 26 IP - 10 DP - 1999 Oct TI - Synovium infiltrating T cells induce excessive synovial cell function through CD28/B7 pathway in patients with rheumatoid arthritis. PG - 2094-101 AB - OBJECTIVE: To clarify involvement of synovial T cells in the development of synovial inflammation in patients with rheumatoid arthritis (RA), we analyzed cellular interactions between synovial cells and infiltrating T cells via CD28/B7-1 and B7-2. METHODS: Synovial cells and infiltrating T cells were recovered separately from RA synovial tissues. Expression of CD28, B7-1, and B7-2 of synovial cells was analyzed by immunohistochemical staining and immunofluorescence analysis. Interleukin 1beta (IL-1beta), IL-6, and matrix metalloprotease 3 (MMP-3) secreted by synovial cells in the presence of infiltrating T cells were measured by ELISA. Nuclear transcription factor CD28 responsive complex was detected by a gel shift assay. RESULTS: Both CD28+ T cells and B7-1/B7-2+ cells were found accumulating in the mononuclear cell infiltrate of RA synovial tissues and B7-1/B7-2+ cells were mainly LeuM3+ synovial cells. CD28 responsive complex was detected in nuclear extracts of freshly isolated lymphocytes from RA synovial tissues, but not those from osteoarthritis synovial tissues or normal peripheral blood, suggesting in vivo activation of T cells by the CD28/B7-1/B7-2 interactions. The irradiated autologous synovium infiltrating T cells notably enhanced IL-1beta, IL-6, and MMP-3 production by the synovial cells. The enhancement of proinflammatory cytokine and MMP-3 production by the synovial cells co-cultured with the T cells was abolished by the addition of CTLA4-Ig, anti-B7-1, and anti-B7-2 monoclonal antibodies. CONCLUSION: These results suggest that cellular interactions between synovium infiltrating T lymphocytes and synovial cells via B7/CD28 pathways are intimately associated with development and exacerbation of inflammation in RA synovial cells. FAU - Shimoyama, Y AU - Shimoyama Y AD - Department of Immunology, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan. FAU - Nagafuchi, H AU - Nagafuchi H FAU - Suzuki, N AU - Suzuki N FAU - Ochi, T AU - Ochi T FAU - Sakane, T AU - Sakane T LA - eng PT - Journal Article PL - Canada TA - J Rheumatol JT - The Journal of rheumatology JID - 7501984 RN - 0 (Antigens, CD) RN - 0 (B7-1 Antigen) RN - 0 (B7-2 Antigen) RN - 0 (CD28 Antigens) RN - 0 (CD86 protein, human) RN - 0 (Membrane Glycoproteins) SB - IM MH - Adult MH - Aged MH - Antigens, CD/immunology/*metabolism MH - Arthritis, Rheumatoid/*immunology/metabolism/pathology MH - B7-1 Antigen/immunology/*metabolism MH - B7-2 Antigen MH - CD28 Antigens/immunology/*metabolism MH - Cell Communication MH - Humans MH - Immunohistochemistry MH - Membrane Glycoproteins/immunology/*metabolism MH - Middle Aged MH - Synovial Membrane/*immunology/metabolism/pathology MH - T-Lymphocytes/immunology/*metabolism EDAT- 1999/10/21 00:00 MHDA- 1999/10/21 00:01 CRDT- 1999/10/21 00:00 PHST- 1999/10/21 00:00 [pubmed] PHST- 1999/10/21 00:01 [medline] PHST- 1999/10/21 00:00 [entrez] PST - ppublish SO - J Rheumatol. 1999 Oct;26(10):2094-101.