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.
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
中文摘要
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.
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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:
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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)
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DOI:
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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:
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发表时间:
期刊:
影响因子:
--
作者:
[]
通讯作者:
シンプル免疫学(中島泉, 高橋利忠, 吉開泰信共著)「感染に対する免疫 免疫の障害 : 免疫不全症」
简单免疫学(中岛泉、高桥利忠、吉凯康信合着)“感染免疫:免疫疾病:免疫缺陷疾病”
DOI:
--
发表时间:
2004
期刊:
影响因子:
--
作者:
[野村 卓正, 光山正雄, 光山正雄, 吉開泰信, 吉開泰信]
通讯作者:
吉開泰信
共 140 条
Host defense against bacterial infection in Notch/IL-7Ralpha axis and CD30L dependent manner.
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批准号:25670213
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项目类别:Grant-in-Aid for Challenging Exploratory Research
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资助金额:$2.5万
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财政年份:2013
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负责人:YOSHIKAI Yasunobu
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依托单位:
The roles of innate T cells in bacterial infection
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批准号:21390130
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项目类别:Grant-in-Aid for Scientific Research (B)
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资助金额:$12.06万
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财政年份:2009
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负责人:YOSHIKAI Yasunobu
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依托单位:
The roles of primitive T cells bearing Toll-like receptor in microbial infection.
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批准号:14370091
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项目类别:Grant-in-Aid for Scientific Research (B)
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资助金额:$9.54万
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财政年份:2002
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负责人:YOSHIKAI Yasunobu
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依托单位:
Analysis for the pathogenesis of concomitant infection in AIDS and murine AIDS
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批准号:10045068
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项目类别:Grant-in-Aid for Scientific Research (B).
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资助金额:$2.05万
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财政年份:1998
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负责人:YOSHIKAI Yasunobu
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依托单位:
Analysis of the molecular mechanisms for early host defense against bacterial infection
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批准号:09470076
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项目类别:Grant-in-Aid for Scientific Research (B)
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资助金额:$6.85万
-
财政年份:1997
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负责人:YOSHIKAI Yasunobu
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依托单位:
The roles of gammadelta T cells in host defense aginst bacterial infection
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批准号:02454191
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项目类别:Grant-in-Aid for General Scientific Research (B)
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资助金额:$4.29万
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财政年份:1990
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负责人:YOSHIKAI Yasunobu
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依托单位:
Analysis of molecular mechanisms of T cell differentiation
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批准号:62480167
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项目类别:Grant-in-Aid for General Scientific Research (B)
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资助金额:$4.22万
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财政年份:1987
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负责人:YOSHIKAI Yasunobu
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依托单位:
海外基金