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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptive Immunity
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Animals
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Bone Marrow Cells
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Bone Marrow Transplantation
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Cell Line, Tumor
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Cytotoxicity, Immunologic
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Dendritic Cells / immunology
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Dendritic Cells / metabolism
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Disease Models, Animal
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Graft vs Host Disease / immunology*
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Humans
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Inflammasomes / immunology*
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Inflammasomes / metabolism
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Interleukin-1beta / immunology
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Interleukin-1beta / metabolism
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Knockout
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NLR Family, Pyrin Domain-Containing 3 Protein / genetics
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NLR Family, Pyrin Domain-Containing 3 Protein / immunology*
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NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
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Neoplasms / immunology*
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Perforin / genetics
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Perforin / immunology
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Perforin / metabolism*
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T-Lymphocytes, Cytotoxic / immunology*
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Xenograft Model Antitumor Assays
Substances
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IL1B protein, mouse
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Inflammasomes
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Interleukin-1beta
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NLR Family, Pyrin Domain-Containing 3 Protein
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NLRP3 protein, human
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Nlrp3 protein, mouse
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PRF1 protein, human
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perforin 1, mouse
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Perforin