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

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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.