Characterization of tissue outgrowth developed in vitro in patients with rheumatoid arthritis: Involvement of T cells in the development of tissue outgrowth

Background: The aim of this study was to analyze cellular and cytokine inte ractions governing the development of synovial tissue outgrowth in patients with rheumatoid arthritis (RA). Methods: A single-cell sus pension of diss ociated synovial tissues of RA patients was cultured for a long period to d evelop tissue outgrowth. The resulting tissue outgrowth was characterized b y immunohistochemical staining and ELISA. Results: The tissue outgrowth dev eloped in vitro included various cell types, such as macrophage-like synovi al cells, fibroblast-like synovial cells and lymphocytes, Even after prolon ged cultivation, synovial cells devoid of infiltrating T lymphocytes did no t form tissue outgrowth. The outgrowth contained CD3+ cells, LeuM3 (CD14)cells and HLA-DR+ cells. The T cells expressed lymphocyte function-associat ed antigen (LFA)-1 and CD2, and the synovial cells expressed intracellular adhesion molecule (ICAM)-1 and LFA-3, suggesting possible interactions via LFA-1/ICAM-1 and CD2/LFA-3. Production of T-cell derived IFN-gamma and IL-1 7 and synovial-cell-derived fibroblast growth factor (FGF)-1 and IL-15 was confirmed in the tissue outgrowth as well as in RA synovial tissue. These c ell types stimulate each other by secreting cytokines, leading to the secre tion of proinflammatory cytokines and matrix metalloproteinase (MMP)-1 by t he tissue outgrowth and proliferation of both lymphocytes and synovial cell s. Conclusion: This study emphasizes the importance of cellular interaction s between T cells and synovial cells, via adhesion molecules and the secret ion of cytokines with stimulatory activity towards other cell types, for th e hyperactivity of RA synovial cells. Copyright (C) 2000 S. Karger AG, Base l.