T cell activation by the exotoxins having superantigenic properties and abonormal reactions observed in patients with the toxin-associated illness.

具有超抗原特性的外毒素激活 T 细胞，并在患有毒素相关疾病的患者中观察到异常反应。

• 批准号: 05807023
• 负责人: IMANISHI Ken'ichi
• 金额: $ 1.15万
• 依托单位: Tokyo Women's Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05807023/
• 关键词: Superantigen; Exotoxin; T cell activation; abnormal reaction; Toxic shock syndrome

Most of bacterial superantigens (SAg), such as toxic shock syndrome toxin-1 (TSST-1), staphylococcal enterotoxins (SE), and streptococcal pyrogenic exotoxins (SPE), are implicated in pathogenesis of certain infectious diseases manifesting acute and systemic clinical symptoms. We have considered that T cell activation by bacterial SAg is primarily involved in the pathogenesis of the infectious diseases caused by these bacteria. We demonstrated that these toxins activate a large number of T cells in a T-cell receptor Vbeta selective way in the presence of accessory cells (AC) expressing MHC class II molecules. The results in this project are as follows :1. The expression of MHC class II molecules on AC is required for SAg-induced TNF-alpha and TNF-beta production in human T cells.2.T cells is much higher than that of CD8^+ T cells is much higher thant that of CD8^+ T cells in SAg-induced TNF-alpha and TNF-beta production.3. IFN-g-stimulated human vascular endothelial cells function as AC for SAg-induced TNF-alpha and TNF-beta production in human T cells.4. We purified and characterized a novel mitogenic substance (YPM) produced by Yersinia pseudotuberculosis isolated from patients manifesting acute and systemic symptoms.5. YPM is a potent T cell activator and has superantigenic properites.

大多数细菌超抗原(SAG)，如中毒性休克综合征毒素-1(TSST-1)、葡萄球菌肠毒素(SE)和链球菌热原外毒素(SPE)等，都与某些表现为急性全身症状的传染病的发病有关。我们认为细菌SAG激活T细胞主要参与了这些细菌引起的感染性疾病的发病机制。我们证明，在表达MHC II类分子的辅助细胞(AC)存在的情况下，这些毒素以T细胞受体Vbeta选择性的方式激活大量的T细胞。本课题的研究结果如下：1.SAG诱导的人T细胞产生肿瘤坏死因子-α和肿瘤坏死因子-β需要AC上MHC-II类分子的表达。2.在SAG诱导的人T细胞产生的肿瘤坏死因子-α和肿瘤坏死因子-β中，T细胞比CD8~+T细胞高得多。干扰素-g刺激的人血管内皮细胞在SAG诱导人T细胞产生肿瘤坏死因子-α和肿瘤坏死因子-β的过程中发挥AC作用。我们从表现急性和全身症状的患者中分离出一种新的有丝分裂物质(YPM)，并对其进行了纯化和鉴定。YPM是一种有效的T细胞激活剂，具有超抗原性。

项目成果

内山竹彦: "Bacterial superantigens-Mechanism of T cell activation by the superantigens and their role in the pathogenesis of infectious dieseas." Microbiol. Immunol.38. 245 (1994)

Takehiko Uchiyama：“细菌超级抗原 - 超级抗原激活 T 细胞的机制及其在微生物学发病机制中的作用。”38 (1994)。

加藤秀人: "Study of TCR Vβ usage in superantigen-reactive human T cells by the RT-PCR method." 東京女子医科大学雑誌. 64. 985 (1994)

Hideto Kato：“通过 RT-PCR 方法研究 TCR Vβ 在超抗原反应性人类 T 细胞中的应用。” 东京女子医科大学学报 64. 985 (1994)。

T.Uchiyama, et al.: "Minireview Bacterial superantigens-Mechanism of T cell activation by the superantigens and their role in the pathogenesis of infectious dieseas." Microbiol.Immunol.38-245. (1994)

T.Uchiyama 等人：“细菌超抗原迷你综述 - 超抗原激活 T 细胞的机制及其在传染性疾病发病机制中的作用。”

今西 健一: "AloctinA,an active substance of Aloe arborecens Miller as an immoromodulator." Phytotherapy Res.7. 20-22 (1993)

Kenichi Imanishi：“AloctinA，木立芦荟的一种活性物质，作为植物疗法 Res.7 (1993)。”

厳 小傑: "Sutdy of activation of marine Tcells with bacterial superantigens." J.Immunel.150. 3873-3881 (1993)

严晓杰：“细菌超抗原激活海洋 T 细胞的研究”，J.Immunel.150 3873-3881 (1993)。