Multiple analysis of the pathogenic mechanism of an re-emerging infectious disease, neonatal TSS-like exanthematous disease and related diseases

1998年，我们阐明了一种超抗原毒素引起的传染病的致病机制，并将这种疾病命名为新生儿tss样疹性疾病（NTED）。在目前的项目中，我们研究了以下科目。1) NTED患者的T细胞反应：急性期TSST- 1反应性T细胞升高至对照水平的3倍，1-2个月后下降至对照水平的20%。扩增状态下的tst -1反应性CD4+ T细胞处于无能状态。存在针对TSST-1的igg型抗体可阻止MRSA新生儿携带者出现临床症状。2)新生儿T细胞的作用：我们获得的数据表明，新生儿T细胞对能量诱导TSST-1的易感性是由于酪氨酸激酶Lck无法与酪氨酸磷酸酶CD45形成功能关联。3)小鼠超抗原诱导的T细胞反应：在小鼠体内植入充满SEA的渗透泵，发现SEA反应的CD4+ T细胞表现出持久的扩张和记忆型反应。4)新型超抗原毒素的发现：我们发现了一种新型超抗原毒素，即半乳不良链球菌衍生的丝裂原，它与抗原呈递细胞上的MHC II类分子联合激活Yβ1 +和Vβ23+ T细胞。

In 1998 we have clarified the pathogenic mechanism of an infectious disease caused by a superantigenic toxin, and designated this disease neonatal TSS-like exanthematous disease (NTED). Under the current project, we examined following subjects.1) T cell response in patients with NTED: TSST- 1-reactive T cells increased to 3-fold the control level in the acute phase and decreased to 20% of the control level 1-2 months later. TSST-1-reactive CD4+ T cells in expanded state are in an anergic state. The presence of IgG-type antibodies to TSST-1 prevented manifestation of clinical symptoms in MRSA neonatal carriers.2) Responsibility of T cell in neonates: We obtained data suggesting that susceptibility of T cells in neonates to anergy induction to TSST-1 is caused by an inability of tyrosine-kinase Lck to make functional association with tyrosine-phosphatase CD45. 3) Superantigen-induced T cell response in mice: Using mice implanted with an osmotic pump filled with SEA, it was found that SEA-reactive CD4+ T cells exhibited protracted expansion and a memory-type response. 4) Discovery of a new type of superantigenic toxin: We found a new type of superantigenic toxin, Streptococcus dysgalactiae-derived mitogen which activates Yβ1 + and Vβ23+ T cells in association with MHC class II molecules on antigenpresenting cells.