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Science. 2012 Feb 24;335(6071):984-9. doi: 10.1126/science.1215418. Epub 2012 Feb 9.

The alarmin interleukin-33 drives protective antiviral CD8⁺ T cell responses.

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Department of Pathology and Immunology, University of Geneva, 1 rue Michel Servet, 1211 Geneva 4, Switzerland.


Pathogen-associated molecular patterns decisively influence antiviral immune responses, whereas the contribution of endogenous signals of tissue damage, also known as damage-associated molecular patterns or alarmins, remains ill defined. We show that interleukin-33 (IL-33), an alarmin released from necrotic cells, is necessary for potent CD8(+) T cell (CTL) responses to replicating, prototypic RNA and DNA viruses in mice. IL-33 signaled through its receptor on activated CTLs, enhanced clonal expansion in a CTL-intrinsic fashion, determined plurifunctional effector cell differentiation, and was necessary for virus control. Moreover, recombinant IL-33 augmented vaccine-induced CTL responses. Radio-resistant cells of the splenic T cell zone produced IL-33, and efficient CTL responses required IL-33 from radio-resistant cells but not from hematopoietic cells. Thus, alarmin release by radio-resistant cells orchestrates protective antiviral CTL responses.

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