CD40 on APCs is needed for optimal programming, maintenance, and recall of CD8+ T cell memory even in the absence of CD4+ T cell help
CD40 on APCs is needed for optimal programming, maintenance, and recall of CD8+ T cell memory even in the absence of CD4+ T cell help
复制标题
DOI：
10.4049/jimmunol.180.7.4382
复制
发表时间：
2008-04-01
影响因子：
4.4
通讯作者：
Rock, Kenneth L.
中科院分区：
文献类型：
--
作者：
Hernandez, Maria Genevive H.;Shen, Lianjun;Rock, Kenneth L.
CD40刺激是激活APC的众多信号之一，我们最近发现它在产生最大的初级CD8（+）T细胞应答中具有独特的功能。然而，CD40信号传导是否在记忆性CD8（+）T细胞应答中起作用仍然没有完全了解。在这项研究中，我们发现，在所有APC或特别是树突状细胞上缺乏CD40的情况下，产生记忆性CD8（+）T细胞，但水平显着降低。这种减少是由于CD40在产生CD8（+）记忆的几个不同步骤中的贡献。在最初的T细胞应答中，CD40不仅有助于最大限度地增加产生的效应细胞的数量，而且还有助于对将分化为记忆的效应细胞进行编程。随后，需要CD40以独立于免疫Ag的方式维持最大数量的定向记忆细胞。最后，当记忆性CD8（+）T细胞被重新激活时，对CD40的需求是可变的，这取决于在初次应答期间是否存在CD40或CD4（+）Th细胞。因此，APC上的CD40信号传导在记忆性CD8（+）T细胞应答的所有阶段中起重要作用。
CD40 stimulation is one of the many signals that can activate APCs and we have recently shown it to have a unique function in generating maximum primary CD8(+) T cell responses. However, whether CD40 signaling plays a role in memory CD8(+) T cell responses is still not completely understood. In this study, we show that in the absence of CD40 on all APCs or specifically on dendritic cells, memory CD8(+) T cells are generated but at significantly reduced levels. This reduction is due to a contribution of CD40 at several different steps in the generation of CD8(+) memory. In the initial T cell response, CD40 contributes to maximizing not only the number of effector cells that are generated but also the programming of ones that will differentiate into memory. Subsequently, CD40 is needed to maintain maximal numbers of the committed memory cells in a manner that is independent of the immunizing Ag. Finally, when memory CD8(+) T cells are reactivated there is a variable requirement for CD40 depending on whether CD40 or CD4(+) Th cells were present during the primary response. Therefore, CD40 signaling on APCs plays an important role in all phases of a memory CD8(+) T cell response.