Antigen-specific CD8+ T cell feedback activates NLRP3 inflammasome in antigen-presenting cells through perforin

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 炎症小体

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作者:Yikun Yao, Siyuan Chen, Mengtao Cao, Xing Fan, Tao Yang, Yin Huang, Xinyang Song, Yongqin Li, Lilin Ye, Nan Shen, Yufang Shi, Xiaoxia Li, Feng Wang, Youcun Qian

Abstract

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.

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