Intracellular signal transduction of Tcell activated with bacterial super-antigen

研究了哺乳动物注射细菌超抗原（SAg）后的生物反应。采用两种典型的细菌sag进行以下实验；中毒性休克综合征毒素-1 （TSST-1）和热毒素A-E （SEs）均来源于葡萄球菌。经SAg预处理的小鼠可诱导对SAg的免疫耐受。在这种状态下，CD4^+ T细胞产生的IL-2被抑制，这种抑制在IL-2替代后被逆转。在系列研究中，我们还发现了维甲酸对T细胞分化的调节作用。新生儿tss样疹性疾病（NTED）的病因尚不清楚，但在系列研究中，我们发现TSST-1在该疾病的发生中起重要作用。虽然病程为皮疹，但预后较好。在此基础上，研究了不同成熟状态下T细胞反应的差异。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的免疫耐受诱导。胸腺细胞和脐带血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通路的研究表明，不同来源的T细胞的CD3-zeta链的甲状腺氨酸磷酸化有显著差异。由于CD3-zeta链是最上游的分子之一，因此这些细胞之间磷酸化水平的差异可能是调节T细胞反应的机制。我们现在正在研究可能参与CD3-zeta链磷酸化的酪氨酸激酶。

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.