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Strategies to control the generation of effective T cell memory.

控制有效 T 细胞记忆生成的策略。

基本信息

批准号：
16043209
负责人：
SAKAMOTO Akemi
金额：
$ 9.6万
依托单位：
Chiba University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16043209/
关键词：
Bc16 memory T cell CD8 Tcell CD4 T cell granzyme B Interferon-g transcriptional factor gene expression 抗原特異的T細胞エフェクターT細胞樹状細胞遺伝子発現制御遺伝子気損マウスウイルス感染 granzyme B

项目摘要

Molecular mechanisms involved in the generation of immune memory cells are largely unknown and their elucidation is the key to design strategies to control the generation of immunity. In this study, w e focused on the role of Bd6 in the memory T cell generation to get better understanding of the mechanisms of generation and maintenance of the memory T cell.1. Role of Bd6 in the generation of memory CD8 T cell and its target geneWe found that Bc16 acts as an amplifier for generation and prolifererative capacity of central memory CD8 T cells. And we also confirmed that granzyme B is a target gene of Bd6 in effector CD8 T cell. As the mechanisms of this regulation, Bd6 recruits histone deacetylase at the promoter of granzyme B and competes against STAT binding using the simmerer sequence for DNA binding. Granzym B is the most important functional molecule, for dearance of virus. But recently, serine protease granzyme B is reported as a factor for inducing suicide of the CD8 T cell itself These data indicate that control of expression of granzyme B by Bc16 is one of the mechanisms for effective memory CD8 T cells.2. Role of Bc16 in the memory CD4 T cell generationCD4 T cell is important to generate functional memory after infection. Bc16 expression is induced in activated CD4 T cells, but the role for Bc16 in the memory CD4 T cells is not known. Then D011.10 back Bc16 deficient mouse were obtained and role of Bc16 during memory CD4 T cells was examined. Bc16 deficient CD4 T cells showed impaired generation of long-term memory CD4 T cells in vivo. From the functional analysis, IFN-y negative CD4 T cells were gradually decreased in Bc16 deficient CD4 T cells. IFN-y negative CD4 T cells include long-lived CD4 T cells. Thus Bc16 is required for the generation and maintenance of long-term memory CD4 T cells,

参与免疫记忆细胞产生的分子机制在很大程度上是未知的，它们的阐明是设计控制免疫产生的策略的关键。本研究主要研究Bd 6在记忆T细胞生成中的作用，以期更好地了解记忆T细胞的生成和维持机制. Bc 16在记忆性CD_8 T细胞生成中的作用及其靶基因我们发现Bc 16在中枢记忆性CD_8 T细胞的生成和增殖能力中起着放大器的作用。我们还证实了颗粒酶B是效应CD 8 T细胞中Bd 6的靶基因。作为这种调节的机制，Bd 6在颗粒酶B的启动子处募集组蛋白脱乙酰酶，并使用simerer序列与STAT竞争结合以用于DNA结合。颗粒酶B是最重要的功能分子，对病毒的灭活具有重要作用。但是最近，丝氨酸蛋白酶颗粒酶B被报道为诱导CD 8 T细胞自身自杀的因子。这些数据表明，Bc 16控制颗粒酶B的表达是有效记忆CD 8 T细胞的机制之一。Bc 16在记忆性CD 4 T细胞生成中的作用感染后，CD 4 T细胞在功能性记忆的生成中起重要作用。Bc 16在活化的CD 4 T细胞中被诱导表达，但Bc 16在记忆性CD 4 T细胞中的作用尚不清楚。然后获得D011.10背部Bc 16缺陷小鼠，并检测Bc 16在记忆性CD 4 T细胞中的作用。Bc 16缺陷型CD 4 T细胞在体内表现出长期记忆性CD 4 T细胞的生成受损。从功能分析，IFN-γ阴性的CD 4 T细胞在Bc 16缺陷型CD 4 T细胞中逐渐减少。IFN-γ阴性CD 4 T细胞包括长寿命的CD 4 T细胞。因此，Bc 16是产生和维持长期记忆性CD 4 T细胞所必需的，