CD4(-CELL-MEDIATED CYTOTOXICITY AGAINST STAPHYLOCOCCAL-ENTEROTOXIN B-PULSED SYNOVIAL-CELLS() T)

Apoptosis of synovial cells in rheumatoid arthritis (RA) synovium dete rmined in vivo is suggested to counteract the overgrowth of synovium. Immunohistological examination has revealed the infiltration of activa ted CD4(+) T cells, which express Fas ligand (FasL), in RA synovium. T he presence of a putative antigen (Ag) of autoimmune disorders in a ta rget organ may induce the activation of specific T cells in the inflam matory region such as RA synovium. We examined the possible role of CD 4(+) T cells activated by synovial cells in a staphylococcal enterotox in B (SEB)-dependent manner, inducing synovial cell apoptosis. Synovia l cells were cultured with or without interferon-gamma (IFN-gamma) and further incubated with CD4(+) T cells in the presence of SEB. After t he cocultivation, both the cytotoxicity and Fast expression of CD4(+) T cells were investigated. Constitutive Fas expression wets detected o n both unstimulated and IFN-gamma-slimulated synovial cells. CD4(+) T cells did not kill SEB-pulsed unstimulated synovial cells efficiently. In contrast, when CD4(+) T cells were incubated with IFN-gamma-stimul ated synovial cells with SEB whose human leucocyte antigen (HLA)-DR an d -DQ expression was markedly induced, significant cytotoxicity by the se 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. Fast expression of CD4(+) T cell s cocultured with IFN-gamma-stimulated synovial cells with SEB was sig nificantly induced. Furthermore. the addition of mAbs against CD54, CD 58 and CD106 inhibited both the cytotoxicity and FasL expression of CD 4(+) T cells induced by IFN-gamma-stimulated synovial cells in the pre sence 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 man ner and express Fast, inducing Fas-mediated apoptosis of the latter ce lls. These phenomena may regulate the overgrowth of synovial cells in RA synovium.