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通过 Clec9A 将抗原靶向小鼠树突状细胞可诱导偏向滤泡辅助表型的强烈 CD4 T 细胞反应。

Targeting antigen to mouse dendritic cells via Clec9A induces potent CD4 T cell responses biased toward a follicular helper phenotype.

机构信息

Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, Victoria 3052, Australia.

出版信息

J Immunol. 2011 Jul 15;187(2):842-50. doi: 10.4049/jimmunol.1101176. Epub 2011 Jun 15.

DOI:10.4049/jimmunol.1101176
PMID:21677141
Abstract

Three surface molecules of mouse CD8(+) dendritic cells (DCs), also found on the equivalent human DC subpopulation, were compared as targets for Ab-mediated delivery of Ags, a developing strategy for vaccination. For the production of cytotoxic T cells, DEC-205 and Clec9A, but not Clec12A, were effective targets, although only in the presence of adjuvants. For Ab production, however, Clec9A excelled as a target, even in the absence of adjuvant. Potent humoral immunity was a result of the highly specific expression of Clec9A on DCs, which allowed longer residence of targeting Abs in the bloodstream, prolonged DC Ag presentation, and extended CD4 T cell proliferation, all of which drove highly efficient development of follicular helper T cells. Because Clec9A shows a similar expression pattern on human DCs, it has particular promise as a target for vaccines of human application.

摘要

三种小鼠 CD8(+)树突状细胞(DC)的表面分子,也存在于等效的人类 DC 亚群中,被比较作为 Ab 介导的 Ag 传递的靶点,这是一种新兴的疫苗接种策略。对于细胞毒性 T 细胞的产生,DEC-205 和 Clec9A 是有效的靶点,但只有在佐剂存在的情况下才有效,而对于 Ab 的产生,Clec9A 则是一个出色的靶点,即使没有佐剂也是如此。强烈的体液免疫是由于 Clec9A 在 DC 上的高度特异性表达所致,这使得靶向 Abs 在血液中的停留时间更长,延长了 DC 呈递 Ag 的时间,并延长了 CD4 T 细胞的增殖,所有这些都促进了滤泡辅助 T 细胞的高效发育。由于 Clec9A 在人类 DC 上表现出相似的表达模式,因此它作为人类应用疫苗的靶点具有特别的前景。

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