Batf3基因缺陷揭示了CD8α⁺树突状细胞在细胞毒性T细胞免疫中的关键作用。
Batf3 deficiency reveals a critical role for CD8alpha+ dendritic cells in cytotoxic T cell immunity.
作者信息
Hildner Kai, Edelson Brian T, Purtha Whitney E, Diamond Mark, Matsushita Hirokazu, Kohyama Masako, Calderon Boris, Schraml Barbara U, Unanue Emil R, Diamond Michael S, Schreiber Robert D, Murphy Theresa L, Murphy Kenneth M
机构信息
Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
出版信息
Science. 2008 Nov 14;322(5904):1097-100. doi: 10.1126/science.1164206.
Abstract
Although in vitro observations suggest that cross-presentation of antigens is mediated primarily by CD8alpha+ dendritic cells, in vivo analysis has been hampered by the lack of systems that selectively eliminate this cell lineage. We show that deletion of the transcription factor Batf3 ablated development of CD8alpha+ dendritic cells, allowing us to examine their role in immunity in vivo. Dendritic cells from Batf3-/- mice were defective in cross-presentation, and Batf3-/- mice lacked virus-specific CD8+ T cell responses to West Nile virus. Importantly, rejection of highly immunogenic syngeneic tumors was impaired in Batf3-/- mice. These results suggest an important role for CD8alpha+ dendritic cells and cross-presentation in responses to viruses and in tumor rejection.
摘要
尽管体外观察表明抗原的交叉呈递主要由CD8α⁺树突状细胞介导，但体内分析因缺乏选择性消除该细胞谱系的系统而受阻。我们发现转录因子Batf3的缺失消除了CD8α⁺树突状细胞的发育，这使我们能够在体内研究它们在免疫中的作用。来自Batf3基因敲除小鼠的树突状细胞在交叉呈递方面存在缺陷，并且Batf3基因敲除小鼠缺乏针对西尼罗河病毒的病毒特异性CD8⁺T细胞反应。重要的是，Batf3基因敲除小鼠对高免疫原性同基因肿瘤的排斥反应受损。这些结果表明CD8α⁺树突状细胞和交叉呈递在病毒反应和肿瘤排斥中起重要作用。
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