Kinetic and mechanistic requirements for helping CD8 T cells
Kinetic and mechanistic requirements for helping CD8 T cells
复制标题
DOI：
10.4049/jimmunol.180.3.1517
复制
发表时间：
2008-02-01
影响因子：
4.4
通讯作者：
Oxenius, Annette
中科院分区：
文献类型：
--
作者：
Agnellini, Paola;Wiesel, Melanie;Oxenius, Annette
产生完全胜任的长寿命记忆CD8 T细胞的要求，特别是CD4 T细胞的作用和帮助机制仍然不明确。在缺乏CD4 T细胞帮助的情况下产生的记忆性CD8 T细胞通常具有受损的回忆增殖，因此无法赋予对某些病原体的保护。然而，提供帮助的时间和机制仍然不清楚，并且在不同的实验系统之间存在差异。在这项研究中，我们研究了CD4 T在一个定义的异源启动-增强系统中帮助产生记忆性CD8 T细胞的作用，该系统由复制能力不足的病毒样颗粒启动和重组痘苗病毒攻击组成，两者只有一个共同的淋巴细胞性脉络丛脑膜炎病毒衍生的CD8 T细胞表位。我们在这个系统中表明，在记忆性CD8 T细胞的回忆增殖的挑战阶段，提供帮助是必不可少的。此外，我们发现，增殖能力强的记忆性CD8 T细胞的产生不依赖于CD40和CCR5，体内IL-2的补充无论是在启动期间还是在挑战期间都不能挽救“未被帮助的”记忆性CD8 T细胞的回忆性增殖。
The requirements for the generation of fully competent long-lived memory CD8 T cells and in particular the role and the mechanisms of help from CD4 T cells remain ill-defined. Memory CD8 T cells generated in the absence of CD4 T cell help often have an impaired recall proliferation and are thus unable to confer protection against certain pathogens. However, the timing and the mechanisms involved in the delivery of help are still unclear and differ between various experimental systems. In this study, we investigated the role of CD4 T help in generating memory CD8 T cells in a defined heterologous prime-boost system, consisting of priming with replication incompetent virus-like particles and challenge with recombinant vaccinia virus, both sharing only a common lymphocytic choriomeningitis virus-derived CD8 T cell epitope. We show in this system that delivery of help is only essential during the challenge phase for recall proliferation of memory CD8 T cells. Furthermore, we show that generation of proliferation-competent memory CD8 T cells is independent of CD40 and CCR5 and that in vivo IL-2 supplementation neither during priming nor during challenge was able to rescue recall proliferation of "unhelped" memory CD8 T cells.