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Bonilla, W.V.* ; Fröhlich, A.* ; Senn, K.* ; Kallert, S.* ; Fernandez, M.* ; Johnson, S.* ; Kreutzfeldt, M.* ; Hegazy, A.N.* ; Schrick, C.* ; Fallon, P.G.* ; Klemenz, R.* ; Nakae, S.* ; Adler, H. ; Merkler, D.* ; Löhning, M.* ; Pinschewer, D.D.*

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

Science 335, 984-989 (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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords CHORIOMENINGITIS VIRUS-INFECTION; IL-1-LIKE CYTOKINE IL-33; IN-VIVO; EFFECTOR FUNCTION; IMMUNE-RESPONSES; MICE; EXPRESSION; RECEPTOR; SIGNALS; ST2
Language english
Publication Year 2012
HGF-reported in Year 2012
ISSN (print) / ISBN 0036-8075
e-ISSN 1095-9203
Journal Science
Quellenangaben Volume: 335, Issue: 6071, Pages: 984-989 Article Number: , Supplement: ,
Publisher American Association for the Advancement of Science (AAAS)
Reviewing status Peer reviewed
Institute(s) Institute of Asthma and Allergy Prevention (IAP)
Research Unit Gene Vector (AGV)
CCG Hematopoetic Cell Transplants (IMI-KHZ)
POF-Topic(s) 30202 - Environmental Health
30203 - Molecular Targets and Therapies
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s) Allergy
Immune Response and Infection
PSP Element(s) G-503300-001
G-501500-006
G-520300-001
DOI 10.1126/science.1215418
WOS ID WOS:000300931800051
Scopus ID 84857640602
PubMed ID 22323740
Erfassungsdatum 2012-03-08
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