Novel mechanisms of selective apoptosis in synovial T cells of patients with rheumatoid arthritis.
OBJECTIVE
To analyze whether T cells infiltrating the synovium of patients with rheumatoid arthritis (RA) express functional Fas antigen.


METHODS
Mononuclear T cells, mainly from synovial tissues, synovial fluids (SF), and peripheral blood mononuclear cells (PBMC) from 14 patients with RA and 5 with osteoarthritis (OA), were treated with anti-Fas monoclonal antibody (Mab) (CH11) for 24 h in vitro. Cell viability and DNA fragmentation were examined. The expression of Fas antigen, Fas ligand, and T cell subpopulations was examined using flow cytometry and reverse transcription polymerase chain reaction.


RESULTS
More than 50% of T cells from synovial tissue and SF of patients with RA underwent apoptosis, whereas no effect was observed in PBMC from RA or PBMC and synovial T cells from OA, suggesting that functional Fas antigens are specifically expressed on synovial T cells. Flow cytometric analysis demonstrated higher expression of Fas antigen in T cells from RA synovium than from PBMC. The T cell subpopulations susceptible to anti-Fas Mab were mainly CD45RO+ and CD4 or CD8 single positive T cells, indicating that activated mature T cells express functional Fas antigen. Fas ligand was overexpressed only in synovial nonadherent cells in RA at the level of mRNA, whereas T cells account for more than 60% of the total, but not in OA.


CONCLUSIONS
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. This phenomenon may provide a clue to understanding the pathogenesis of RA.
Hoa
T T
TT
Division of Rheumatology and Immunology, St. Marianna University School of Medicine, Kawasaki, Japan.
Hasunuma
T
T
Aono
H
H
Masuko
K
K
Kobata
T
T
Yamamoto
K
K
Sumida
T
T
Nishioka
K
K
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001483:Base Sequence; D015139:Blotting, Southern; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008875:Middle Aged; D010003:Osteoarthritis / Q000276:immunology; D016133:Polymerase Chain Reaction; D013582:Synovial Fluid / Q000276:immunology*; D013583:Synovial Membrane / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D019014:fas Receptor / Q000032:analysis*
D000911:Antibodies, Monoclonal; D019014:fas Receptor