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Analysis of mechanisms of T cell activation by exotoxins bearing superantigenic properties and induction of abnormal changes by them.

分析具有超抗原特性的外毒素激活 T 细胞的机制及其诱导异常变化的机制。

基本信息

批准号：
05454196
负责人：
UCHIYAMA Takehiko
金额：
$ 4.1万
依托单位：
Tokyo Women's Medical College
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05454196/
关键词：
superantigen T cells MHC class ll molecules lymphokines TCR Vbeta elements TSS YPM Vβエレメント MHCクラスII 細菌感染症

项目摘要

Several of bacterial superantigens are known as pathogenic exotoxins of infectious diseases such as toxic shock syndrome (TSS), scarlet fever and Yersinia pseudotuberculosis infection. These exotoxins, which did not have any apparent cytotoxic activity to various kinds of cells so far invetigated, activate of massive T cell populatious in a TCRVbeta-specific way to produce large amounts of lymhokines. We consider that the overproduction of lymhokines resulting from overactivation of T cells by them are involved primarily in development of abnormal reactions observed in these infectious diseases. We obtained following experimental results during the part two years.1. We found a novel superantigenic exotoxin (Y.pseudotuberculosis-derived mitogen, YPM) from Y.pseudotuberculosis strains which were isolated from patients with Y.pseudotuberculosis infection. YPM consits of 131 amino acid residues.2. YPM in a combined injection with D-galactosamine induced lethal shock in C57BL/6 mice in a CD4^+ T cell-dependent way. TNF-alpha seems to be involved in generation of YPM-induced shock.3. Staphylococcal enterotoxin A (SEA) in a acombined injection with D-galactosamine induced lethal shock in C57BL/6 mice in a CD4^+ T cell-depended way.

几种细菌超抗原被称为传染病的致病性外毒素，例如中毒性休克综合征（TSS）、猩红热和假结核耶尔森菌感染。这些外毒素迄今为止对各种细胞没有任何明显的细胞毒活性，但它们以 TCRVbeta 特异性方式激活大量 T 细胞，产生大量淋巴因子。我们认为，由于 T 细胞过度激活而导致淋巴因子的过量产生，这主要与这些传染病中观察到的异常反应的发生有关。经过两年多的时间，我们得到了以下实验结果： 1．我们从假结核杆菌感染患者体内分离出的假结核杆菌菌株中发现了一种新型超抗原外毒素（假结核杆菌衍生丝裂原，YPM）。 YPM由131个氨基酸残基组成。2． YPM 与 D-半乳糖胺联合注射以 CD4^+ T 细胞依赖性方式诱导 C57BL/6 小鼠致死性休克。 TNF-α似乎参与了YPM引起的休克的产生。3．葡萄球菌肠毒素 A (SEA) 与 D-半乳糖胺联合注射以 CD4^+ T 细胞依赖性方式在 C57BL/6 小鼠中诱导致死性休克。