Report

RIPK1 and NF-κB signaling in dying cells determines cross-priming of CD8+ T cells

See allHide authors and affiliations

Science  16 Oct 2015:
Vol. 350, Issue 6258, pp. 328-334
DOI: 10.1126/science.aad0395

You are currently viewing the abstract.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

Dying to impress the immune system

Besides reacting to microbes, T cells can also mount immune responses to fragments of dying cells, which they encounter displayed on dendritic cells. Not all dying cells activate T cells, however, so what differentiates the dying cells that do? Yatim et al. studied two forms of programmed cells death: apoptosis and necroptosis. Using mouse cells in culture and mouse models of inflammatory cell death and anti-tumor immunity, they found that programmed cell death initiated T cell immunity only when the dying cells signaled through the enzyme RIPK1 and the transcription factor NF-κB.

Science, this issue p. 328

Abstract

Dying cells initiate adaptive immunity by providing both antigens and inflammatory stimuli for dendritic cells, which in turn activate CD8+ T cells through a process called antigen cross-priming. To define how different forms of programmed cell death influence immunity, we established models of necroptosis and apoptosis, in which dying cells are generated by receptor-interacting protein kinase-3 and caspase-8 dimerization, respectively. We found that the release of inflammatory mediators, such as damage-associated molecular patterns, by dying cells was not sufficient for CD8+ T cell cross-priming. Instead, robust cross-priming required receptor-interacting protein kinase-1 (RIPK1) signaling and nuclear factor κB (NF-κB)–induced transcription within dying cells. Decoupling NF-κB signaling from necroptosis or inflammatory apoptosis reduced priming efficiency and tumor immunity. Our results reveal that coordinated inflammatory and cell death signaling pathways within dying cells orchestrate adaptive immunity.

View Full Text