Antigen-specific CD8(+) T cell feedback activates NLRP3 inflammasome in antigen-presenting cells through perforin.
Antigen-specific CD8(+) T cell feedback activates NLRP3 inflammasome in antigen-presenting cells through perforin.
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抗原特异性 CD8( ) T 细胞反馈通过穿孔素激活抗原呈递细胞中的 NLRP3 炎性体
DOI：
10.1038/ncomms15402
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发表时间：
2017-05-24
影响因子：
16.6
通讯作者：
Qian Y
中科院分区：
文献类型：
--
作者：
Yao Y;Chen S;Cao M;Fan X;Yang T;Huang Y;Song X;Li Y;Ye L;Shen N;Shi Y;Li X;Wang F;Qian Y
先天免疫和获得性免疫之间的联系最好的例证是抗原呈递。虽然抗原提呈细胞(APC)是抗原受体介导的T细胞活化所必需的，但T细胞如何反馈到APC以维持抗原特异性免疫反应尚不完全清楚。在这里，我们发现CD8+T细胞(也称为细胞毒性T淋巴细胞)反馈以抗原依赖的方式激活APC中的NLRP3炎性小体，促进IL-1β的成熟。APC中NLRP3炎症体的激活需要来自抗原特异性CTL的穿孔素。此外，NLRP3炎症体的这种激活有助于诱导抗原特异性的抗肿瘤免疫和移植物抗宿主病的发病。我们的研究揭示了抗原特异性CTL和APC之间的正反馈循环，以放大获得性免疫。穿孔素是CD8+T细胞细胞毒效应机制的一部分。在这里，作者证明了抗原诱导的穿孔素从CD8T细胞释放到抗原提呈细胞，可以激活NLRP3炎症体，构成一个正反馈环路，促进抗肿瘤免疫和同种异体反应。
The connection between innate and adaptive immunity is best exemplified by antigen presentation. Although antigen-presenting cells (APCs) are required for antigen receptor-mediated T-cell activation, how T-cells feedback to APCs to sustain an antigen-specific immune response is not completely clear. Here we show that CD8+ T-cell (also called cytotoxic T lymphocytes, CTL) feedback activates the NLRP3 inflammasome in APCs in an antigen-dependent manner to promote IL-1β maturation. Perforin from antigen-specific CTLs is required for NLRP3 inflammasome activation in APCs. Furthermore, such activation of NLRP3 inflammasome contributes to the induction of antigen-specific antitumour immunity and pathogenesis of graft-versus-host diseases. Our study reveals a positive feedback loop between antigen-specific CTLs and APC to amplify adaptive immunity. Perforin is part of the cytotoxic effector mechanism of CD8+ T cells. Here the authors show that antigen-induced perforin release from CD8 T cells into antigen-presenting cells can activate NLRP3 inflammasome to constitute a positive feedback loop to promote anti-tumour immunity and allo-responses.