DEFICIENT FAS LIGAND EXPRESSION BY SYNOVIAL LYMPHOCYTES FROM PATIENTSWITH RHEUMATOID-ARTHRITIS

Objective. To examine the expression and function of CD95 (Fas) and it s 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 whethe r lymphocytes could undergo Fas-mediated apoptosis with anti-CD95 mono clonal antibody (MAb) or human Fas ligand-expressing fibroblasts, and if synovial fluid contained a soluble factor(s) that could inhibit suc h interactions. Finally, we determined whether anti-CD3 MAb could indu ce synovial T cells to express the Fas ligand in vitro. Results, Nearl y 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 Ri synovial fluid that could accoun t for the survival of CD95+ synovial cells in vivo, Instead, we detect ed little or no expression of Fas ligand by RA synovial lymphocytes. H owever, we could induce such cells to express Fas ligand with anti-CD3 MAb or phorbol ester and ionomycin in vitro. Conclusion. There is ine ffective clearance of activated cells in the RA joint due to deficient expression of the Fas ligand.