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

Bonilla, Weldy V; Fröhlich, Anja; Senn, Karin; Kallert, Sandra; Fernandez, Marylise; Johnson, Susan; Kreutzfeldt, Mario; Hegazy, Ahmed N; Schrick, Christina; Fallon, Padraic G; Klemenz, Roman; Nakae, Susumu; Adler, Heiko; Merkler, Doron; Löhning, Max; Pinschewer, Daniel

doi:10.1126/science.1215418

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Title		The alarmin interleukin-33 drives protective antiviral CD8+ T cell responses
Authors		Bonilla, Weldy V Fröhlich, Anja Senn, Karin Kallert, Sandra Fernandez, Marylise Johnson, Susan Kreutzfeldt, Mario Hegazy, Ahmed N Schrick, Christina Fallon, Padraic G Klemenz, Roman Nakae, Susumu Adler, Heiko Merkler, Doron Löhning, Max Pinschewer, Daniel show all authors [1 - 16]
Published in		Science. 2012, vol. 335, no. 6071, p. 984-9
Abstract		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.
Keywords		Adoptive Transfer — Animals — Arenaviridae Infections/immunology/pathology — Cell Differentiation — Gene Expression Profiling — Herpesviridae Infections/immunology — Interleukins/genetics/immunology/metabolism — Lymphocyte Activation — Lymphocytic choriomeningitis virus/immunology/physiology — Mice — Mice, Transgenic — Necrosis — Receptors, Interleukin/genetics/metabolism — Recombinant Proteins/immunology — Rhadinovirus/immunology — Signal Transduction — Stromal Cells/immunology/metabolism — T-Lymphocytes, Cytotoxic/immunology/transplantation — Tumor Virus Infections/immunology — Up-Regulation — Vaccinia virus/immunology — Virus Replication
Identifiers		DOI: 10.1126/science.1215418 PMID: 22323740
Full text		Article (Published version) (1.2 MB) - Limited access to UNIGE
Structures		Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie
Research groups		Infections virales persistantes et maladies autoimmunes (849) La Sclérose en plaques (908)
Citation (ISO format)		BONILLA, Weldy V et al. The alarmin interleukin-33 drives protective antiviral CD8+ T cell responses. In: Science, 2012, vol. 335, n° 6071, p. 984-9. doi: 10.1126/science.1215418 https://archive-ouverte.unige.ch/unige:28431