4.8 Article

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

Journal

NATURE COMMUNICATIONS
Volume 8, Issue -, Pages -

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms15402

Keywords

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Funding

  1. National Natural Science Foundation of China [81430036, 81230075, 91429307, 91329301, 91542119, 31329002, 31400756]
  2. 973 Program [2013CB944904]
  3. Chinese Academy of Sciences [XDB19000000]
  4. China Postdoctoral Science Foundation [2014M551471]

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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-1 beta 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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