The shift of immune-response and memory T cell differentiation induced by superantigens.

超抗原(SAG)具有不依赖于抗原特异性而激活T细胞的能力，从而产生大量的细胞因子。在SAG诱导的激活后，T细胞进入无能状态，典型的特征是产生IL-2的缺陷。我们研究了SAG刺激诱导记忆T细胞分化的可能性，以及无能和记忆诱导机制的差异。我们得到了以下结果。1)建立了OVA-TCR转基因小鼠(OVA23-3)和TSST-1的体内无能诱导体系。2)正常抗原OVA可诱导高水平IL-6的细胞因子风暴，对OVA23-3细胞的免疫应答包括IgG1的产生产生一过性抑制。3)TSST-1在体内和体外诱导细胞因子风暴，包括IL-2和IL-6。TSST-1二次刺激可诱导T细胞无能，而OVA刺激不能诱导T细胞无能。4)OVA刺激和TSST-1刺激可促进IL-2启动子区组蛋白H3乙酰化，而TSST-1再刺激可抑制组蛋白H3乙酰化，而OVA再刺激未见此作用。5)无能T细胞表达记忆标记和激活标记，提示无能T细胞具有记忆T细胞的某些特征。

Superantigens(sAg) possess an, ability to activate T cells independent of antigen-specificity, resulting in producing a huge amount of cytokines. After the activation induced by sAg, T cells fall into anergy state typically characterized by the defect for producing IL-2. We investigated the possibility of memory T cell differentiation by sAg stimulation and the difference of the mechanism between anergy and memory induction. We obtained the following results. 1) The system of in vivo anergy induction was established using OVA-TCR-transgenic mouse (OVA23-3) and TSST-1. 2) Normal antigen OVA could induce cytokine storm with high level of IL-6, which transiently suppressed immune-response including IgG1 production in OVA23-3. 3) TSST-1 induced cytokine storm including IL-2 and IL-6 in vivo and in vitro. Secondary stimulation with TSST-1 induced T cell anergy while OVA stimulation did not induce it. 4) OVA-stimulation and TSST-1 stimulation induced enhanced histone H3 acetylation of IL-2 promoter region, while re-stimulation by TSST-1 induced suppression of histone H3 acetylation which is not observed by OVA re-stimulation. 5) Memory markers and activation markers were expressed on anergic T cells, which suggested, that anergic T cells possess some characters of memory T cells.