The Alarmin Interleukin-33 Drives Protective Antiviral CD8+T Cell Responses.
Bonilla, Weldy V. 1,2,*; Frohlich, Anja 3,4,*; Senn, Karin 5,*; Kalltert, Sandra 1,2; Fernandez, Marylise 1,2; Johnson, Susan 1,2; Kreutzfeldt, Mario 1,6; Hegazy, Ahmed N. 3,4,7; Schrick, Christina 1,6; Fallon, Padraic G. 8; Klemenz, Roman 5; Nakae, Susumu 9; Adler, Heiko 10; Merkler, Doron 1,6,11; Lohning, Max 3,4,+; Pinschewer, Daniel D. 1,2,+
[Article]
Science.
335(6071):984-989, February 24, 2012.
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: 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.
Copyright (C) 2012 by the American Association for the Advancement of Science