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

重新出现的传染病、新生儿TSS样疹病及相关疾病发病机制的多重分析

基本信息

批准号：
11470072
负责人：
UCHIYAMA Takehiko
金额：
$ 8.77万
依托单位：
Tokyo Woman's Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

项目摘要

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.

1998年，我们阐明了由超抗原毒素引起的感染性疾病的致病机制，并将这种疾病命名为新生儿TSS样外生性疾病（NTED）。在本项目中，我们研究了以下主题：1）NTED患者的T细胞反应：TSST- 1反应性T细胞在急性期增加到对照水平的3倍，1-2个月后下降到对照水平的20%。扩增状态的TSST-1反应性CD 4 + T细胞处于无反应性状态。抗TSST-1 IgG型抗体的存在可预防MRSA新生儿携带者的临床症状。2）新生儿T细胞的反应性：我们获得的数据表明，新生儿T细胞对TSST-1无反应性诱导的易感性是由酪氨酸激酶Lck无法与酪氨酸磷酸酶CD 45进行功能性关联引起的。3)小鼠中超抗原诱导的T细胞应答：使用植入充满SEA的渗透泵的小鼠，发现SEA反应性CD 4 + T细胞表现出延长的扩增和记忆型应答。4)一种新型超抗原毒素的发现：我们发现了一种新型的超抗原毒素，停乳链球菌（Streptococcus dysgalactiae）衍生的丝裂原（mitogen），它能激活与抗原提呈细胞上的MHC Ⅱ类分子相关的Yβ1 +和Vβ23+ T细胞。