Systemic inflammatory response elicited by superantigen destabilizes T regulatory cells, rendering them ineffective during toxic shock syndrome.
Systemic inflammatory response elicited by superantigen destabilizes T regulatory cells, rendering them ineffective during toxic shock syndrome.
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DOI：
10.4049/jimmunol.1400980
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发表时间：
2014-09-15
期刊：
影响因子：
--
通讯作者：
Rajagopalan G
中科院分区：
文献类型：
--
作者：
Tilahun AY;Chowdhary VR;David CS;Rajagopalan G
由金黄色葡萄球菌引起的危及生命的感染，特别是社区获得的耐甲氧西林金黄色葡萄球菌菌株（CA-MRSA），继续造成严重问题。某些金黄色葡萄球菌菌株的毒力增强和致病性增强归因于外毒素的较高流行。在这些外毒素中，超抗原 (SAg) 可能是最具致病性的，因为它们即使在极少量的情况下也能够快速、有力地激活 T 细胞。因此，使用 T 调节细胞 (Treg) 对抗 SAg 介导的 T 细胞激活可能对中毒性休克综合征 (TSS) 等疾病有益。由于典型宿主中内源性Tregs的正常数量不足，我们假设通过施用IL2-抗IL2抗体复合物（IL2C）或通过离体扩增的Tregs的过继转移来增加Tregs数量可能更有效地对抗SAg介导的免疫激活。与人类 TSS 非常相似的 HLA-DR3 转基因小鼠接受 IL2C 处理以增加内源性 Tregs 或接受离体扩增的 Tregs。随后，他们接受 SAg 激发以诱导 TSS。对反映 TSS 的各种参数（血清细胞因子/趋化因子水平、多器官病理学和 SAg 诱导的外周 T 细胞扩增）的分析表明，增加 Tregs 未能减轻 TSS。相反，IL2C治疗小鼠的血清IFN-γ水平升高。对 Tregs 缺乏保护作用背后原因的探索揭示了 TSS 期间 IL-17 和 IFN-γ 依赖性 Tregs 的丢失。此外，TSS期间传统T细胞上GITR的显着上调可能使它们对Treg介导的抑制产生抵抗，从而导致Treg介导的免疫调节失败。
Life-threatening infections caused by Staphylococcus aureus, particularly the community-acquired methicillin-resistant strains of S. aureus (CA-MRSA), continue to pose serious problems. Greater virulence and increased pathogenicity of certain S. aureus strains are attributed to higher prevalence of exotoxins. Of these exotoxins, the superantigens (SAg) are likely most pathogenic because of their ability to rapidly and robustly activate the T cells even in extremely small quantities. Therefore, countering SAg-mediated T cell activation using T regulatory cells (Tregs) might be beneficial in diseases such as toxic shock syndrome (TSS). As the normal numbers of endogenous Tregs in a typical host are insufficient, we hypothesized that increasing the Treg numbers by administration of IL2-anti-IL2 antibody complexes (IL2C) or by adoptive transfer of ex vivo expanded Tregs might be more effective in countering SAg-mediated immune activation. HLA-DR3 transgenic mice that closely recapitulate human TSS, were treated with IL2C to increase endogenous Tregs or received ex vivo expanded Tregs. Subsequently, they were challenged with SAg to induce TSS. Analyses of various parameters reflective of TSS (serum cytokine/chemokine levels, multiple organ pathology and SAg-induced peripheral T cell expansion) indicated that increasing the Tregs failed to mitigate TSS. On the contrary, serum IFN-γ levels were increased in IL2C treated mice. Exploration into the reasons behind the lack of protective effect of Tregs revealed IL-17 and IFN-γ-dependent loss of Tregs during TSS. In addition, significant upregulation of GITR on conventional T cells during TSS could render them resistant to Treg mediated suppression, contributing to failure of Treg-mediated immune regulation.
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影响因子：
32.4
作者：
Bailey-Bucktrout, Samantha L.;Martinez-Llordella, Marc;Zhou, Xuyu;Anthony, Bryan;Rosenthal, Wendy;Luche, Herve;Fehling, Hans J.;Bluestone, Jeffrey A.
通讯作者：
Bluestone, Jeffrey A.
DOI：
10.1073/pnas.0909384107
发表时间：
2010-02-02
影响因子：
11.1
作者：
Letourneau, Sven;van Leeuwen, Ester M. M.;Boyman, Onur
通讯作者：
Boyman, Onur
影响因子：
4.4
作者：
Ji, HB;Liao, GX;Terhorst, C
通讯作者：
Terhorst, C
影响因子：
11.2
作者：
Cao X;Leonard K;Collins LI;Cai SF;Mayer JC;Payton JE;Walter MJ;Piwnica-Worms D;Schreiber RD;Ley TJ
通讯作者：
Ley TJ
DOI：
10.4049/jimmunol.0903412
发表时间：
2010-01-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Caretto D;Katzman SD;Villarino AV;Gallo E;Abbas AK
通讯作者：
Abbas AK