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.
Highlights
The connection between innate and adaptive immunity is best exemplified by antigen presentation
We compared the ability of CTLs and the other remaining cells in the mixed-lymphocyte reaction (MLR) to induce IL-1b production in bone marrow-derived dendritic cells (BMDCs) and found that CTLs were the predominant cells for IL-1b secretion and target cell killing (Fig. 1k; Supplementary Fig. 1e)
We found that IL-1b secretion was already highly induced in the supernatant of BMDCs that were treated with only perforin buffer (Fig. 4j), likely due to the high extracellular calcium concentration in the buffer because calcium is reported to be essential for NLRP3 activation[37] and the calcium inhibitor or NLRP3 deficiency blocked the buffer-induced IL-1b secretion (Fig. 4j)
Summary
The connection between innate and adaptive immunity is best exemplified by antigen presentation. We show that CD8 þ T-cell ( called cytotoxic T lymphocytes, CTL) feedback activates the NLRP3 inflammasome in APCs in an antigen-dependent manner to promote IL-1b maturation. Our study reveals a positive feedback loop between antigen-specific CTLs and APC to amplify adaptive immunity. One study reported that anti-CD3-activated T cells dampen innate immune responses through suppressing the NLRP3 inflammasome in macrophages in an antigenindependent manner[24]. It is not completely clear how innate immunity-driven adaptive immunity feedback promotes innate immunity to amplify antigen-specific immune responses. We show that CTLs activate the NLRP3 inflammasome in APCs which amplifies antigen-specific CTL-mediated effector functions
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