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

一些细菌超抗原被称为感染性疾病的致病外毒素，如中毒性休克综合征(TSS)、猩红热和假结核耶尔森菌感染。到目前为止，这些外毒素对各种细胞没有任何明显的细胞毒活性，它们以TCRVβ特异的方式激活大量的T细胞，产生大量的淋巴因子。我们认为淋巴因子的过度产生是由T细胞过度激活引起的，这主要与在这些传染病中观察到的异常反应的发生有关。在两年的时间里，我们取得了以下实验结果。我们从假结核分支杆菌感染者分离的假结核分支杆菌中发现了一种新的超抗原外毒素(YPm)。YPM由131个氨基酸残基组成。YPM联合D-氨基半乳糖可诱导C57BL/6小鼠致死性休克，其作用依赖于T细胞。肿瘤坏死因子-α似乎参与了YPM诱导的休克的发生。葡萄球菌肠毒素A(SEA)联合D-氨基半乳糖诱导C57BL/6小鼠致死性休克，其作用依赖于T细胞。

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.