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Intracellular signal transduction of Tcell activated with bacterial super-antigen

细菌超抗原激活T细胞的胞内信号转导

基本信息

批准号：
08670320
负责人：
FUJIMAKI Wakae
金额：
$ 1.41万
依托单位：
Tokyo Women's Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670320/
关键词：
Bacterial super-antigen T-cell signal transduction

项目摘要

Biological rensponses after administration of bacterial super-antigen (SAg) into mammal were studied. Two typical bacterial SAgs were used for the following experiments ; toxic shock syndrome toxin -1 (TSST-1) and enthelotoxin A-E (SEs) which were derived from staphylococcus. Immunotolerance to SAg can be induced in mice pretreated with SAg. In this state, IL-2 production from CD4^+ T cell were suppressed and this suppression was reversed after IL-2 replacement. in the serial study, we also found that T cell differentiation was modulated by retinoic acid.The cause of neonatal TSS-like exanthematous disease (NTED) has not been known, but in the serial study, we found that TSST-1 play an important role in developing this disease. Although the course of the disease is rash, the prognosis is relatively favorable. Based on these findings, the difference in the T cell response according to their maturation status was studied. Induction of immunotolerance in human derived cells were studied in mature thymic cells, in T cells from cord blood and in peripheral T cells. Immunotolerance were more easily induced in thymic cells and in T cells from cord blood than peripheral T cells.Study on signal transduction pathway in these cells revealed that thyrosine phosphorylation of CD3-zeta chain was remarkably different among these T cells from different origin. It is considered that the difference of the phophorylation level among these cells is the possible mechanism which regulates the T cell response since the CD3-zeta chain is one of the most upstream molecules. We are now examining the tyrosine kinases which might be involved in the CD3-zeta chain phosphorylation.

研究了细菌超抗原（SAg）对哺乳动物的生物学反应。两种典型的细菌SAg用于以下实验：中毒性休克综合征毒素-1（TSST-1）和源自大肠杆菌的内毒素A-E（SE）。SAg预处理可诱导小鼠产生免疫耐受。在这种状态下，CD 4 ^+ T细胞产生IL-2受到抑制，这种抑制在IL-2替代后被逆转。在系列研究中，我们还发现T细胞分化受视黄酸的调节，新生儿TSS样外显症（NTED）的病因尚不清楚，但在系列研究中，我们发现TSST-1在NTED的发生发展中起重要作用。虽然病程皮疹，但预后相对较好。基于这些发现，研究了根据其成熟状态的T细胞应答的差异。在成熟胸腺细胞、脐带血T细胞和外周血T细胞中研究了人源性细胞中免疫耐受的诱导。胸腺细胞和脐血T细胞比外周血T细胞更容易诱导免疫耐受，对这些细胞信号转导途径的研究表明，不同来源的T细胞CD 3-zeta链的甲状腺素磷酸化程度存在显著差异。由于CD 3-zeta链是最上游的分子之一，因此认为这些细胞之间磷酸化水平的差异是调节T细胞应答的可能机制。我们现在正在研究可能参与CD 3-zeta链磷酸化的酪氨酸激酶。