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CD4 + T‐cell‐mediated cytotoxicity against staphylococcal enterotoxin B‐pulsed synovial cells
Author(s) -
Atsushi Kawakami,
Naoki Matsuoka,
Masahiko Tsuboi,
Satoshi Urayama,
Tomoki Nakashima,
Yojiro Kawabe,
Takehiko Koji,
Takahiko Aoyagi,
Kenji Maeda,
Katsumi Eguchi
Publication year - 1998
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1998.00569.x
Subject(s) - synovial membrane , cytotoxicity , microbiology and biotechnology , cytotoxic t cell , fas ligand , antigen , apoptosis , immunology , t cell , chemistry , biology , in vitro , arthritis , immune system , programmed cell death , biochemistry
Apoptosis of synovial cells in rheumatoid arthritis (RA) synovium determined in vivo is suggested to counteract the overgrowth of synovium. Immunohistological examination has revealed the infiltration of activated CD4 + T cells, which express Fas ligand (FasL), in RA synovium. The presence of a putative antigen (Ag) of autoimmune disorders in a target organ may induce the activation of specific T cells in the inflammatory region such as RA synovium. We examined the possible role of CD4 + T cells activated by synovial cells in a staphylococcal enterotoxin B (SEB)‐dependent manner, inducing synovial cell apoptosis. Synovial cells were cultured with or without interferon‐γ (IFN‐γ) and further incubated with CD4 + T cells in the presence of SEB. After the cocultivation, both the cytotoxicity and FasL expression of CD4 + T cells were investigated. Constitutive Fas expression was detected on both unstimulated and IFN‐γ‐stimulated synovial cells. CD4 + T cells did not kill SEB‐pulsed unstimulated synovial cells efficiently. In contrast, when CD4 + T cells were incubated with IFN‐γ‐stimulated synovial cells with SEB whose human leucocyte antigen (HLA)‐DR and ‐DQ expression was markedly induced, significant cytotoxicity by these cells against synovial cells was detected. The addition of anti‐HLA‐DR and ‐DQ monoclonal antibodies (mAbs) or human Fas chimeric protein (hFas‐Fc) reduced this cytotoxicity. FasL expression of CD4 + T cells cocultured with IFN‐γ‐stimulated synovial cells with SEB was significantly induced. Furthermore, the addition of mAbs against CD54, CD58 and CD106 inhibited both the cytotoxicity and FasL expression of CD4 + T cells induced by IFN‐γ‐stimulated synovial cells in the presence of SEB, indicating the importance of costimulatory molecules on synovial cells in activating CD4 + T cells. Our results suggest that CD4 + T cells are activated by synovial cells by an SEB‐dependent manner and express FasL, inducing Fas‐mediated apoptosis of the latter cells. These phenomena may regulate the overgrowth of synovial cells in RA synovium.