Effects of superantigen and lipopolysaccharide on induction of CD80 through apoptosis of human monocytes.
To investigate the mechanisms underlying superantigen (SAg) stimulation, we analyzed the effect of SAg on monocyte responses with or without lipopolysaccharide (LPS). Addition of gamma interferon (IFN-gamma) to unstimulated cultures induced a marked increase in the number of CD80(+) monocytes, which was inhibited by LPS through the action of interleukin-10. However, CD80(+) monocytes began to increase before IFN-gamma production, observed after 9 h of stimulation with staphylococcal enterotoxin B (SEB). SEB selectively increased the number of apoptotic CD80(-) monocytes, whereas LPS-treated monocytes were resistant to the apoptotic action of SEB. This SEB-induced killing was abrogated by anti-CD95 monoclonal antibody (MAb) ZB4 and anti-CD95 ligand (CD95L) MAb NOK2, suggesting a CD95-based pathway of apoptosis. Furthermore, the numbers of SEB-induced CD80(+) monocytes were partially decreased by anti-CD119 (IFN-gamma receptor) MAb and by anti-CD95L (NOK2) MAb. The CD30 expression of CD27(high) T cells induced by SEB was increased by agonistic anti-CD95 (CH11) MAb. Together, our findings showed that SEB-induced monocyte apoptosis is closely associated with the enrichment of CD80(+) monocytes generated before IFN-gamma production, followed by up-regulation of CD80 by IFN-gamma, and that LPS has negative effects in both cases. These results also suggested that induction of monocyte apoptosis is an important mechanism by which SAg exerts its anti-inflammatory effects.
Takahashi
M
M
Department of Microbiology and Immunology, Tohoku University School of Dentistry, Aoba-ku, Sendai 980-8575, Japan.
Takahashi
M
M
Shinohara
F
F
Takada
H
H
Rikiishi
H
H
D017209:Apoptosis / Q000276:immunology*; D018122:B7-1 Antigen / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004768:Enterotoxins / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008213:Lymphocyte Activation; D009000:Monocytes / Q000276:immunology*; D018089:Superantigens / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors
D018122:B7-1 Antigen; D016207:Cytokines; D004768:Enterotoxins; D008070:Lipopolysaccharides; D018089:Superantigens; C031818:enterotoxin B, staphylococcal; D007371:Interferon-gamma