학술논문
Culling of APCs by inflammatory cell death pathways restricts TIM3 and PD-1 expression and promotes the survival of primed CD8 T cells.
Document Type
Academic Journal
Author
Patel R; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.; Kim K; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.; Shutinoski B; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.; Wachholz K; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.; National Research Council of Canada, Ottawa, Ontario, Canada.; Krishnan L; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.; National Research Council of Canada, Ottawa, Ontario, Canada.; Sad S; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Source
Publisher: Nature Publishing Group Country of Publication: England NLM ID: 9437445 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5403 (Electronic) Linking ISSN: 13509047 NLM ISO Abbreviation: Cell Death Differ Subsets: MEDLINE
Subject
Language
English
Abstract
We evaluated the impact of premature cell death of antigen-presenting cells (APCs) by Caspase-1- and RipK3-signaling pathways on CD8 + T-cell priming during infection of mice with Salmonella typhimurium (ST). Our results indicate that Caspase1 and RipK3 synergize to rapidly eliminate infected APCs, which does not influence the initial activation of CD8 + T cells. However, the maintenance of primed CD8 + T cells was greatly compromised when both these pathways were disabled. Caspase-1- and RipK3-signaling did not influence NF-κB signaling in APCs, but synergized to promote processing of IL-1 and IL-18. Combined deficiency of Caspase1 and RipK3 resulted in compromised innate immunity and accelerated host fatality due to poor processing of IL-18. In contrast, synergism in cell death by Caspase-1- and RipK3 resulted in restriction of PD-1 and TIM3 expression on primed CD8 + T cells, which promoted the survival of activated CD8 + T cells.