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TRAIL/DR5 在 NK 细胞介导的树突状细胞交叉呈递 T 细胞的负调控中起着关键作用。

TRAIL/DR5 plays a critical role in NK cell-mediated negative regulation of dendritic cell cross-priming of T cells.

机构信息

Department of Microbiology and Immunology, Dartmouth Medical School, Lebanon, NH 03756, USA.

出版信息

J Immunol. 2011 Sep 15;187(6):3087-95. doi: 10.4049/jimmunol.1003879. Epub 2011 Aug 10.

DOI:10.4049/jimmunol.1003879
PMID:21832159
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3169733/
Abstract

Dendritic cells (DCs) are critical in initiating immune responses by cross-priming of tumor Ags to T cells. Previous results showed that NK cells inhibited DC-mediated cross-presentation of tumor Ags both in vivo and in vitro. In this study, enhanced Ag presentation was observed in draining lymph nodes in TRAIL(-/-) and DR5(-/-) mice compared with that of wild-type mice. NK cells inhibit DC cross-priming of tumor Ags in vitro, but not direct presentation of endogenous Ags. NK cells lacking TRAIL, but not perforin, were not able to inhibit DC cross-priming of tumor Ags. DCs that lack expression of TRAIL receptor DR5 were less susceptible to NK cell-mediated inhibition of cross-priming, and cross-linking of DR5 receptor led to reduced generation of MHC class I-Ag peptide complexes, followed by attenuated cross-priming of CD8(+) T cells. In addition, key molecules involved in the TRAIL/DR5 pathway during DC/NK cell interactions were determined. In summary, these data indicate a novel alternative pathway for DC/NK cell interactions in antitumor immunity and may reflect homeostasis of both DCs and NK cells for regulation of CD8(+) T cell function in physiological conditions.

摘要

树突状细胞 (DCs) 通过交叉呈递肿瘤抗原来激活 T 细胞，从而在启动免疫反应中起关键作用。先前的结果表明，NK 细胞在体内和体外均抑制 DC 介导的肿瘤抗原交叉呈递。在这项研究中，与野生型小鼠相比，TRAIL(-/-)和 DR5(-/-)小鼠引流淋巴结中的抗原呈递增强。NK 细胞在体外抑制 DC 对肿瘤抗原的交叉呈递，但不抑制内源性抗原的直接呈递。缺乏 TRAIL 但不缺乏穿孔素的 NK 细胞不能抑制 DC 对肿瘤抗原的交叉呈递。缺乏 TRAIL 受体 DR5 表达的 DC 对 NK 细胞介导的交叉呈递抑制的敏感性降低，DR5 受体交联导致 MHC Ⅰ类-Ag 肽复合物的生成减少，随后 CD8(+) T 细胞的交叉呈递减弱。此外，还确定了 DC/NK 细胞相互作用过程中 TRAIL/DR5 途径中的关键分子。总之，这些数据表明了 DC/NK 细胞相互作用在抗肿瘤免疫中的一种新的替代途径，可能反映了 DC 和 NK 细胞在生理条件下调节 CD8(+) T 细胞功能的自身平衡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb87/3169733/79e5dbcf3a6f/nihms312001f9.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb87/3169733/79e5dbcf3a6f/nihms312001f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb87/3169733/44eaeb81b3f5/nihms312001f1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb87/3169733/79e5dbcf3a6f/nihms312001f9.jpg

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