Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
Key Laboratory of Stem Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences &Shanghai Jiaotong University School of Medicine, Shanghai 200031, China.
Nat Commun. 2017 May 24;8:15402. doi: 10.1038/ncomms15402.
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.
先天免疫和适应性免疫之间的联系在抗原呈递中表现得最为明显。尽管抗原呈递细胞（APCs）是抗原受体介导的 T 细胞激活所必需的，但 T 细胞如何反馈给 APC 以维持抗原特异性免疫反应尚不完全清楚。在这里，我们表明 CD8 T 细胞（也称为细胞毒性 T 淋巴细胞，CTL）以抗原依赖性方式反馈激活 APC 中的 NLRP3 炎性小体，以促进 IL-1β 的成熟。来自抗原特异性 CTL 的穿孔素对于 APC 中 NLRP3 炎性小体的激活是必需的。此外，这种 NLRP3 炎性小体的激活有助于诱导抗原特异性抗肿瘤免疫和移植物抗宿主病的发病机制。我们的研究揭示了抗原特异性 CTL 和 APC 之间的正反馈回路，以放大适应性免疫。
