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

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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.