首页> 外文期刊>American Journal of Physiology >Deficiency of gammadelta T lymphocytes contributes to mortality and immunosuppression in sepsis.
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Deficiency of gammadelta T lymphocytes contributes to mortality and immunosuppression in sepsis.

机译:γT淋巴细胞不足会导致败血症的死亡率和免疫抑制。

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Studies have indicated that gammadelta T lymphocytes play an important role in the regulation of immune function and the clearance of intracellular pathogens. We have recently reported that intraepithelial lymphocytes (IEL), which are rich in gammadelta T cells, within the small intestine illustrated a significant increase in apoptosis and immune dysfunction in mice subjected to sepsis. However, the contribution of gammadelta T cells to the host response to polymicrobial sepsis remains unclear. In this study, we initially observed that after sepsis induced by cecal ligation and puncture (CLP), there was an increase in small intestinal IEL CD8+gammadelta+ T cells in control gammadelta+/+ mice. Importantly, we subsequently found an increased early mortality in mice lacking gammadelta T cells (gammadelta-/- mice) after sepsis. This was associated with decreases in plasma TNF-alpha, IL-6, and IL-12 levels in gammadelta-/- mice compared with gammadelta+/+ mice after sepsis. In addition, even though in vitroLPS-stimulated peritoneal macrophages showed a reduction in IL-6 and IL-12 release after CLP, these cytokines were less suppressed in macrophages isolated from gammadelta-/- mice. Alternatively, IL-10 release was not different between septic gammadelta+/+ and gammadelta-/- mice. Whereas T helper (Th)1 cytokine release by anti-CD3-stimulated splenocytes was significantly depressed in septic gammadelta+/+ mice, there was no such depression in gammadelta-/- mice. However, gammadelta T cell deficiency had no effect on Th2 cytokine release. These findings suggest that gammadelta T cells may play a critical role in regulating the host immune response and survival to sepsis, in part by alteration of the level of IEL CD8+gammadelta+ T cells and through the development of the Th1 response.
机译:研究表明,γT淋巴细胞在调节免疫功能和清除细胞内病原体中起重要作用。我们最近报道,小肠内富含γδT细胞的上皮内淋巴细胞(IEL)说明败血症小鼠的凋亡和免疫功能异常显着增加。然而,伽马δT细胞对宿主对多菌血症的反应的贡献尚不清楚。在这项研究中,我们最初观察到盲肠结扎和穿刺(CLP)诱发败血症后,对照伽马δ+ / +小鼠小肠IEL CD8 +伽马δ+ T细胞有所增加。重要的是,我们随后发现败血症后缺乏γ-δT细胞的小鼠(γ-/-小鼠)的早期死亡率增加。与败血症后的gammadelta + / +小鼠相比,gammadelta-/-小鼠的血浆TNF-α,IL-6和IL-12水平降低与之相关。此外,即使体外LPS刺激的腹膜巨噬细胞在CLP后显示IL-6和IL-12释放减少,但从γ-/-小鼠分离的巨噬细胞中这些细胞因子的抑制作用却较小。或者,在败血性γ+ / +和γ-/-小鼠之间IL-10的释放没有差异。在败血性γ+ / +小鼠中,抗CD3刺激的脾细胞释放的T辅助(Th)1细胞因子显着降低,而在γ-/-小鼠中没有这种降低。但是,γT细胞缺乏对Th2细胞因子释放没有影响。这些发现表明,γδT细胞可能在调节宿主免疫应答和败血症生存中起关键作用,部分原因是通过改变IEL CD8 +γδ+ T细胞的水平以及通过Th1应答的发展。

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