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Studies on differentiation, maturation and activation of human T cells

人类T细胞分化、成熟和活化的研究

基本信息

批准号：
10670272
负责人：
IMANISHI Ken'ichi
金额：
$ 2.11万
依托单位：
Tokyo Women's Medical University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670272/
关键词：
T cells differentiation maturation activation superantigen 胸腺臍帯血アナジー

项目摘要

1. We examined the responses of different stages of CD4 single positive (SP) T cells to a superantigen, TSST-1. The following results were obtained. (1) Thymic CD1a^-CD4 SP T cells are functionally mature, but CD1a^+CD4 SP T cells are not. (2) Thymic CD1a^- and cord blood (CB) CD4^+ T cells are susceptible to anergy induction, while adult peripheral blood (APB) CD4^+ T cells are not. The susceptibility to it is higher in thymic T cells than in CB T cells. (3) The majority of thymic and CB T cells are CD38^+, while CD38 expression in APB T cells is varied. Both APB CD38^+ and CD38^- CD4^+ T cells are not susceptible to anergy induction. (4) APB CD38^+CD4^+ T cells are weak in a potential to produce IL-4 and IFN-γ, while CD38^- T cells have the high potential. These results suggest that post-thymic maturation is required for thymic T cells migrating to the periphery to acquire full immunologic capability to the antigenic stimulation.2. Studies on signal transduction in thymic and APB CD4 … More ^+ T cells suggest that absence of an interaction between Lck and CD45 is responsible for maintaining the anergic state of thymic CD1a^- CD4^+ T cells induced by TSST-1.3. We discovered an emerging neonatal infectious disease, neonatal toxic shock syndrome-like exanthematous disease (NTED), which is induced by TSST-1 produced by methicilllin-resistant Staphylococcus aureus (MRSA). Then, we analyzed the activation and the response of TSST-1-reactive Vβ2^+ T cells in NTED patients during the acute and recovery phases and in asymptomatic infants exposed to MRSA.In the acute phase, Vβ2^+ T cells were anergic to stimulation with TSST-1 and underwent marked expansion, but by 2 months after disease onset, their number had declined to about 10% of the control level. On the basis of Vβ2^+ T cells activation, asymptomatic neonatal MRSA carriers were divided to two types ; type 1, Vβ2^+ T cells were activated by TSST-1 ; type 2, Vβ2^+ T cells were intact. We also observed protective role of anti-TSST-1 IgG of maternal origin against the influence of TSST-1. Less

1.我们研究了不同阶段的CD 4单阳性（SP）T细胞的超抗原，TSST-1的反应。获得了以下结果。(1)胸腺CD 1a ^-CD 4 SP T细胞功能成熟，而CD 1a ^+ CD 4 SP T细胞功能不成熟。(2)胸腺CD 1a ^-和脐带血（CB）CD 4 ^+ T细胞对无反应性诱导敏感，而成人外周血（APB）CD 4 ^+ T细胞则不敏感。胸腺T细胞比CB T细胞对它的易感性更高。(3)大多数胸腺和CB T细胞是CD 38 ^+，而APB T细胞中的CD 38表达是不同的。APB CD 38 ^+和CD 38 ^-CD 4 ^+ T细胞对无反应性诱导均不敏感。(4)APB CD 38 ^+ CD 4 ^+ T细胞产生IL-4和IFN-γ的潜力较弱，而CD 38 ^- T细胞具有较高的潜力。这些结果表明，胸腺后成熟是胸腺T细胞迁移到外周以获得对抗原刺激的完全免疫能力所必需的.胸腺和APB细胞CD 4信号转导的研究 ...更多信息 ^+ T细胞表明Lck和CD 45之间缺乏相互作用是维持TSST-1.3诱导的胸腺CD 1a ^-CD 4 ^+ T细胞无反应性状态的原因。我们发现了一种新生儿感染性疾病，新生儿中毒性休克综合征样外展性疾病（NTED），它是由耐甲氧西林金黄色葡萄球菌（MRSA）产生的TSST-1诱导的。然后，我们分析了NTED患者急性期和恢复期以及暴露于MRSA的无症状婴儿中TSST-1反应性Vβ2^+ T细胞的活化和反应，在急性期，Vβ2^+ T细胞对TSST-1刺激无反应性，并发生显著扩增，但在疾病发作后2个月，其数量下降至对照水平的约10%。根据Vβ2^+ T细胞活化情况，新生儿MRSA无症状携带者可分为两种类型：1型，Vβ2^+ T细胞被TSST-1激活; 2型，Vβ2^+ T细胞完整。我们还观察到母体来源的抗TSST-1 IgG对TSST-1影响的保护作用。少