THE FUNCTIONAL CD40 ANTIGEN OF FIBROBLASTS MAY CONTRIBUTE TO THE PROLIFERATION OF RHEUMATOID SYNOVIUM

This paper demonstrates that CD40 is expressed on rheumatoid synovial pannus and primary fibroblast cell lines established from rheumatoid a nd osteoarthritic synovium as well as normal skin. Among various teste d cytokines, interferon-gamma (IFN-gamma) and to a lower extent, tumou r necrosis factor-alpha (TNF-alpha) were found to upregulate CD40 expr ession on fibroblasts. Synovial and skin fibroblasts cultured over CD4 0 Ligand transfected L cells (L-CD40 L) demonstrate a CD40 specific in crease of DNA synthesis as measured by tritiated thymidine incorporati on. Cell-cycle analysis and enumeration of viable cells further show t hat CD40 induced fibroblast proliferation. Costimulation with L-CD40 L and IFN-gamma resulted in maximal proliferation. Engagement of fibrob lasts CD40 increased the IL-1-induced production of granulocyte macrop hage-colony stimulating factor and macrophage inflammatory protein-1 a lpha MIP-1 alpha. CD40 L activated fibroblasts showed decreased levels of CD40, but only marginal alterations of other cell-surface antigens . Taken together, the present results indicate that fibroblasts expres s functional CD40 and suggest a possible role of CD40 L expressing cel ls, such as activated T cells and mast cells, in the development of sy novium hyperplasia.