Priming of CTLs by lymphocytic choriomeningitis virus depends on dendritic cells

Priming of CTLs by lymphocytic choriomeningitis virus depends on dendritic cells
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DOI:
10.4049/jimmunol.174.7.3920
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发表时间:
2005-04-01
影响因子:
4.4
通讯作者:
van den Broek, M
van den Broek, M
中科院分区:
医学2区
文献类型:
--
作者:
Probst, HC;van den Broek, M

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初始CD8(+) T细胞的适当激活取决于这些细胞与专业APC的协调相互作用,APC在MHC I类分子的背景下呈现抗原肽。树突状细胞(DC)在激活初始T细胞方面是有效的,并且在启动CD8(+) T细胞应答外源性细胞相关Ags方面具有独特的能力。然而,目前尚不清楚源自内源性合成蛋白并由MHC I类分子呈递到其他APC(包括B细胞和巨噬细胞)表面的表位是否能在体内激活初始CD8(+) T细胞。通过用淋巴细胞性脉络丛脑膜炎病毒(LCMV)感染转基因CD11c-DTR/GFP小鼠,使DC有条件衰竭,LCMV感染所有类型的APC并引发强烈的CTL反应,我们明确地表明,LCMV特异性CD8(+) T细胞的启动至关重要地依赖于DC,尽管在次级淋巴器官中存在大量LCMV感染的巨噬细胞和B细胞。
Appropriate activation of naive CD8(+) T cells depends on the coordinated interaction of these cells with professional APC that present antigenic peptides in the context of MHC class I molecules. It is accepted that dendritic cells (DC) are efficient in activating naive T cells and are unique in their capacity to prime CD8(+) T cell responses against exogenous cell-associated Ags. Nevertheless, it is unclear whether epitopes, derived from endogenously synthesized proteins and presented by MHC class I molecules on the surface of other APC including B cells and macrophages, can activate naive CD8(+) T cells in vivo. By infecting transgenic CD11c-DTR/GFP mice that allow conditional depletion of DC with lymphocytic choriomeningitis virus (LCMV), which infects all types of APC and elicits a vigorous CTL response, we unambiguously show that priming of LCMV-specific CD8(+) T cells is crucially dependent on DC, despite ample presence of LCMV-infected macrophages and B cells in secondary lymphoid organs.