Antigen-specific CD8<sup>+</sup> T cell feedback activates NLRP3 inflammasome in antigen-presenting cells through perforin.

Yao, Yikun; Chen, Siyuan; Cao, Mengtao; Fan, Xing; Yang, Tao; Huang, Yin; Song, Xinyang; Li, Yongqin et al. · Nat Commun · 2017

basic_science · Level V

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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<sup>+</sup> 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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