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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。

基本信息

批准号：
13226036
负责人：
YOSHIKAI Yasunobu
金额：
$ 38.78万
依托单位：
Kyushu University (2002-2005)Nagoya University (2001)
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
起止时间：
2001 至 2005
项目状态：
已结题

项目摘要

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.

在细胞内病原体的急性感染过程中，抗原特异性T细胞在扩张期增殖，然后大多数T细胞在随后的收缩期凋亡死亡，但少数存活的T细胞成为记忆细胞并长期存在。记忆性CD8T细胞被迅速激活以抵抗再次感染并消灭病原体。通过将表达OVA_<257-264>/K^b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，然后用表达OVA的重组单核增生李斯特菌攻毒，我们发现IL-15在记忆性CD8T细胞的产生、维持和再激活中的作用如下：(1)效应期：细菌感染后，IL-15在效应性CD8T细胞的产生中是不可缺少的。(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CD8 +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CD8 + T细胞的长期维持中发挥重要作用。(4)再激活：IL-15在再次感染时通过诱导细胞毒性分子，在记忆性CD8 + T细胞的早期激活中发挥重要作用。