DUAL ROLES FOR CLASS-II MAJOR HISTOCOMPATIBILITY COMPLEX-MOLECULES IN STAPHYLOCOCCAL ENTEROTOXIN-INDUCED CYTOKINE PRODUCTION AND INVIVO TOXICITY

被引:43
作者
GROSSMAN, D
LAMPHEAR, JG
MOLLICK, JA
BETLEY, MJ
RICH, RR
机构
[1] BAYLOR COLL MED, DEPT MICROBIOL & IMMUNOL, HOUSTON, TX 77030 USA
[2] BAYLOR COLL MED, DEPT MED, HOUSTON, TX 77030 USA
[3] UNIV WISCONSIN, DEPT BACTERIOL, MADISON, WI 53706 USA
关键词
D O I
10.1128/IAI.60.12.5190-5196.1992
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The staphylococcal enterotoxins (SE) specifically bind to class 11 major histocompatibility complex (MHC) proteins, resulting in activation of monocytes and T cells. The SE cause weight loss in mice, which is dependent on T-cell stimulation and tumor necrosis factor alpha (TNF-alpha) production. Here we use a mutant of staphylococcal enterotoxin A that binds class II MHC molecules and activates monocytes but not T cells to evaluate the relative contributions of monocyte- and T-cell-stimulatory activities to in vivo toxicity. The mutant toxin did not cause weight loss in B10.BR mice but did stimulate monocyte TNF-alpha production in vitro, as did the wild-type toxin. Addition of a supernatant from toxin-activated T cells enhanced monocyte-stimulatory activity of both mutant and wild-type toxins fivefold. The effect of the supernatant could be mimicked by recombinant gamma interferon (IFN-gamma) and was inhibited by antibody to IFN-gamma. These results suggest that toxin-induced monocyte TNF-alpha production is upregulated by IFN-gamma, which likely represents the T-cell requirement in SE-mediated weight loss. Our studies thus implicate two distinct class II MHC-dependent signaling pathways for SE, the first involving direct signal transduction through class II MHC molecules mediated by either mutant or wild-type toxin and the second requiring T-cell stimulation by toxin-class II MHC complexes with consequent production of IFN-gamma. We suggest that both pathways are required for optimal monocyte TNF-alpha production in vitro and SE-induced toxicity in vivo.
引用
收藏
页码:5190 / 5196
页数:7
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