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Molecular mechanisms for generation and maintenance of memory CD8T cells following bacterial infection.

Molecular mechanisms for generation and maintenance of memory CD8T cells following bacterial infection.
细菌感染后记忆 CD8T 细胞生成和维持的分子机制。
批准号:
13226036
负责人:
YOSHIKAI Yasunobu
金额:
$38.78万
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:
2001
资助国家:
日本
项目状态:
已结题
起止时间:
2001 至 2005

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中文摘要
翻译
在细胞内病原体的急性感染过程中,抗原特异性T细胞在扩增期增殖,然后大多数T细胞在随后的收缩期因凋亡而死亡,但少数存活的T细胞成为记忆细胞并持续很长一段时间。记忆性CD 8 T细胞被迅速激活以抵抗再感染并消除病原体。通过将表达OVA_1<257-264>/K_1b特异性T细胞受体的OT-I细胞过继转移到对照、IL-15敲除(KO)和IL-15转基因(Tg)小鼠中,然后用表达OVA的重组单核细胞增生李斯特菌(Listeria monocytogenes)攻击,我们发现IL-15在记忆性CD_8 T细胞的产生、维持和再活化中的作用如下:(1)效应期:IL-15在细菌感染后被激活以产生效应性CD_8 T细胞。(2)收缩期:IL-15通过诱导抗凋亡分子在微生物感染后的收缩期保护效应CD 8 ^+T细胞免于凋亡中起关键作用。(3)维持期:IL-15通过诱导稳态增殖在记忆性CD 8 ^+ T细胞的长期维持中发挥重要作用。(4)再活化:IL-15通过诱导再感染时的细胞毒性分子,在记忆性CD 8 ^+ T细胞的早期活化中发挥重要作用。
英文摘要
During the course of acute infection with an intracellular pathogen, antigen-specific T cells proliferate in the expansion phase, and then most of the T cells die by apoptosis in the following contraction phase, but the few that survive become memory cells and persist for a long period of time. Memory CD8T cells are activated rapidly against re-infection and eliminate pathogens. Using an adoptive transfer system of OT-I cells expressing OVA_<257-264>/K^b-specific T cell receptor into control, IL-15 knockout (KO) and IL-15 transgenic (Tg) mice followed by challenge with recombinant Listeria monocytogenes expressing OVA, we found the roles of IL-15 in generation, maintenance and reactivation of memory CD8T cells as follows :(1) Effector phase : IL-15 is dispensable for generation of effector CD8T cells following bacterial infection.(2) Contraction phase : IL-15 plays a critical role in protecting effector CD8^+T cells from apoptosis during the contraction phase following a microbial infection via inducing anti-apoptotic molecules.(3) Maintenance phase : IL-15 plays an important role in long-term maintenance of memory CD8^+ T cells through induction of homeostatic proliferation.(4) Reactivation : IL-15 plays an important role in early activation of memory CD8^+ T cells through induction of cytotoxic molecules upon re-infection.
期刊论文(336)
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会议论文
A serine/threonine kinase, Cot/Tp12,modulates bacterial DNA-induced IL-12 production and Th cell differentiation
丝氨酸/苏氨酸激酶 Cot/Tp12 调节细菌 DNA 诱导的 IL-12 产生和 Th 细胞分化
DOI: --
发表时间: 2004
期刊: J Clin Invest. 114
影响因子: --
作者: [Sugimoto K, et al.]
通讯作者: et al.
Enforced expression of Bcl-2 restores numbers but not functions of TCRgd intestinal intraepithelial T lymphocytes in IL-15-deficient mice
Bcl-2 的强制表达可恢复 IL-15 缺陷小鼠中 TCRgd 肠上皮内 T 淋巴细胞的数量,但不能恢复其功能
DOI: --
发表时间: 2007
期刊: J. Immunol. 178
影响因子: --
作者: [Nakazato K., Yamada H., Yajima T., Kagimoto Y., Kuwano H., Yoshikai Y]
通讯作者: Yoshikai Y
Yajima, T., et al.: "Overexpression of IL-15 in vivo Increases antigen-driven memory CD8+T cells following a microbe exposure"J. Immunol.. 168. 1198-2003 (2002)
Yajima, T. 等人:“体内 IL-15 的过度表达会增加微生物暴露后抗原驱动的记忆 CD8 T 细胞的数量”J.
DOI: --
发表时间:
期刊:
影响因子: --
作者: []
通讯作者:
Umemura, M.: "Overexpression of IL-15 in vivo induces a predominant Tcl response in mice inoculated with Mycobacterium bovis Bacille Calmette-Guerin infection"J. Immunol.. 167. 946-956 (2001)
Umemura, M.:“体内 IL-15 的过度表达会在接种牛分枝杆菌卡介苗感染的小鼠中诱导主要的 Tcl 反应”J.
DOI: --
发表时间:
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影响因子: --
作者: []
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共 140 条
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