Deficient Fas ligand expression by synovial lymphocytes from patients with rheumatoid arthritis

Abstract

OBJECTIVE: To examine the expression and function of CD95 (Fas) and its ligand in rheumatoid arthritis (RA). METHODS: We used flow cytometry and reverse transcriptase-polymerase chain reaction methods to assess lymphocyte expression of CD95 and its ligand. We also examined whether lymphocytes could undergo Fas-mediated apoptosis with anti-CD95 monoclonal antibody (MAb) or human Fas ligand-expressing fibroblasts, and if synovial fluid contained a soluble factor(s) that could inhibit such interactions. Finally, we determined whether anti-CD3 MAb could induce synovial T cells to express the Fas ligand in vitro. RESULTS: Nearly all RA synovial fluid or synovial tissue lymphocytes expressed CD95 and could be induced to undergo apoptosis by CD95 crosslinking. We did not detect a soluble inhibitor in RA synovial fluid that could account for the survival of CD95+ synovial cells in vivo. Instead, we detected little or no expression of Fas ligand by RA synovial lymphocytes. However, we could induce such cells to express Fas ligand with anti-CD3 MAb or phorbol ester and ionomycin in vitro. CONCLUSION: There is ineffective clearance of activated cells in the RA joint due to deficient expression of the Fas ligand.