In vivo depletion of CD11c+ dendritic cells abrogates priming of CD8+ T cells by exogenous cell-associated antigens
In vivo depletion of CD11c+ dendritic cells abrogates priming of CD8+ T cells by exogenous cell-associated antigens
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DOI：
10.1016/s1074-7613(02)00365-5
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发表时间：
2002-08-01
期刊：
影响因子：
32.4
通讯作者：
Lang, RA
中科院分区：
文献类型：
--
作者：
Jung, S;Unutmaz, D;Lang, RA
细胞毒性T淋巴细胞(CTL)对MHC-I类分子上的抗原肽产生反应。在大多数细胞中，这些多肽完全来自内源性、胞浆来源。然而，骨髓来源的抗原提呈细胞对外源抗原的MHC I提呈有独特的途径。这一机制允许病原体感染细胞的交叉呈现和针对细胞内微生物感染的CTL反应的启动。在这里，我们报告了一种新的基于白喉毒素的系统，它允许在体内诱导的、短期的树突状细胞(DC)消融。我们发现，在体内，DC需要与CTL前体交叉启动。因此，我们的结果确定了DC在体内的独特作用，即免疫系统对细胞相关抗原的敏化。DC耗尽的小鼠开始对细胞内单核细胞增生性李斯特氏菌和啮齿动物疟疾寄生虫约氏疟原虫的感染产生CTL反应。
Cytotoxic T lymphocytes (CTL) respond to antigenic peptides presented on MHC class I molecules. On most cells, these peptides are exclusively of endogenous, cytosolic origin. Bone marrow-derived antigen-presenting cells, however, harbor a unique pathway for MHC I presentation of exogenous antigens. This mechanism permits cross-presentation of pathogen-infected cells and the priming of CTL responses against intracellular microbial infections. Here, we report a novel diphtheria toxin-based system that allows the inducible, short-term ablation of dendritic cells (DC) in vivo. We show that in vivo DC are required to cross-prime CTL precursors. Our results thus define a unique in vivo role of DC, i.e., the sensitization of the immune system for cell-associated antigens. DC-depleted mice fall to mount CTL responses to infection with the intracellular bacterium Listeria monocytogenes and the rodent malaria parasite Plasmodium yoelii.