Immunohistologic analysis of the distribution of cell adhesion molecules within the inflammatory synovial microenvironment

Abstract

Antigen-independent binding of T lymphocytes to a variety of cell types has been shown to be mediated by receptor-ligand pairs of adhesion molecules. In forms of inflammatory synovitis (including rheumatoid arthritis), T cells home to synovium, become activated, and participate in the generation of chronic synovitis. Using indirect immunofluorescence assays on synovial frozen tissue sections and on synovial fibroblast cell lines, we studied the distribution of cell adhesion molecules on components of the synovial microenvironment in inflammatory synovitis. We reasoned that analysis of the cell types within synovium that express adhesion molecules might provide clues to lymphocyte-stromal interactions that occur in inflammatory synovitis. We found that antibodies against the lymphocyte function-associated antigen 3 (LFA-3) molecule and the intercellular adhesion molecule 1 (ICAM-1) both reacted with macrophage-like type A synovial cells and synovial fibroblasts, as well as with tissue macrophages and vessel endothelium. Using flow cytometry, we found that anti-LFA-3 and anti-ICAM-1 (but not antibodies against their ligands CD2 and LFA-1) reacted with synovial fibroblast cells cultured in vitro. Thus, these data demonstrate that the ligands for lymphocyte LFA-1 molecules (ICAM-1) and for T cell CD2 molecules (LFA-3) are widely distributed among cell types of the synovial microenvironment and provide numerous cell types with which lymphocytes can interact via these 2 adhesion pathways during the course of inflammatory synovitis.