Intracellular signal transduction of Tcell activated with bacterial super-antigen

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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.