NOVEL MECHANISMS OF SELECTIVE APOPTOSIS IN SYNOVIAL T-CELLS OF PATIENTS WITH RHEUMATOID-ARTHRITIS

Objective. To analyze whether T cells infiltrating the synovium of pat ients with rheumatoid arthritis (RA) express functional Fas antigen. M ethods. Mononuclear T cells, mainly from synovial tissues, synovial fl uids (SF), and peripheral blood mononuclear cells (PBMC) from 14 patie nts with RA and 5 with osteoarthritis (OA), were treated with anti-Fas monoclonal antibody (Mab) (CH11) for 24 h in vitro. Cell viability an d DNA fragmentation were examined. The expression of Fas antigen, Fas ligand, and T cell subpopulations was examined using flow cytometry an d reverse transcription polymerase chain reaction. Results. More than 50% of T cells from synovial tissue and SF of patients with RA underwe nt apoptosis, whereas no effect was observed in PBMC from RA or PBMC a nd synovial T cells from OA, suggesting that functional Fas antigens a re specifically expressed on synovial T cells. Flow cytometric analysi s demonstrated higher expression of Fas antigen in T cells from RA syn ovium than from PBMC. The T cell subpopulations susceptible to anti-Fa s Mab were mainly CD45RO+ and CD4 or CD8 single positive T cells, indi cating that activated mature T cells express functional Fas antigen. F as ligand was overexpressed only in synovial nonadherent cells in RA a t the level of mRNA, whereas T cells account for more than 60% of the total, bur not in OA. Conclusion. These findings suggest the majority of activated T cells infiltrating the synovium express functional Fas antigen and Fas ligand specifically in patients with RA but not OA. Th is phenomenon may provide a clue to understanding the pathogenesis of RA.