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

Article Article scientifique Article The alarmin interleukin-33 drives protective antiviral CD8+ T cell responses eng 2012 author Bonilla Weldy V author Fröhlich Anja author Senn Karin author Kallert Sandra 736317 author Fernandez Marylise 668367 author Johnson Susan 681717 author Kreutzfeldt Mario 736806 author Hegazy Ahmed N author Schrick Christina 741796 author Fallon Padraic G author Klemenz Roman author Nakae Susumu author Adler Heiko author Merkler Doron 735735 author Löhning Max author Pinschewer Daniel 663530 984-989 10.1126/science.1215418 22323740 0036-8075 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. 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 Dewey 616.07 137 Département de pathologie et immunologie 21F false 511 Infections virales persistantes et maladies autoimmunes 849 565 La Sclérose en plaques 908 Science 335 6071 d4778a12-b512-4593-8a5e-c51c0a87456a Article (Published version) Restricted Merkler D Science 2012,335(6071)984.pdf 1242718 application/pdf restrictedAccess Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie

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The alarmin interleukin-33 drives protective antiviral CD8+ T cell responses	Science	2012	733	0

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Kallert, Sandra