Induction of Fas-dependent apoptosis in synovial infiltrating cells in rheumatoid arthritis

Apoptosis is a feature of the synovium of rheumatoid arthritis(RA). We have recently shown that RA synoviocytes were susceptibleto anti-Fas mAb and undergo apoptosis in vitro. To investigatewhether infiltrating mononuclear cells also undergo Fas-dependentapoptosis, double-labeling techniques combined with immunohistochemicalexamination with anti-CD3 mAb and the TdT-mediated dUTP-biotinnick end labeling (TUNEL) method to detect apoptotic cells,or in situ RT assay to detect Fas mRNA, were performed usingfrozen tissue sections. We also examined the in vitro inductionof Fas-dependent apoptosis in freshly isolated synovium infiltratingmononuclear cells (SIM), synovial stromal cells (SSC) and peripheralblood lymphocytes (PBL) using tissues from nine patients withRA and three with osteoarthritis (OA). The results showed expressionof Fas antigen and apoptotic cells in a number of CD3-bearingcells in RA synovial tissues. In vitro treatment with anti-FasmAb produced a significant apoptosis of RA SIM and SSC, whilenone of PBL, and neither SIM nor SSC from OA exhibited apoptosis.Moreover, 50% of CD4⁺, CD3⁺ and CD45RO⁺ cells, and >90% ofFas-expressing cells of RA SIM underwent apoptosis in responseto anti-Fas mAb, as detected by flow cytometry. Our resultssuggest that RA synovial infiltrating lymphocytes acquire highsusceptibility to anti-Fas mAb and undergo apoptosis. Such aphenomenon of infiltrating T cells in RA synovium may play animportant pathophysiological role and suggest a possible therapeuticeffect for anti-Fas mAb in RA.