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

Bonilla, Weldy V
Fröhlich, Anja
Senn, Karin
Hegazy, Ahmed N
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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 TransferAnimalsArenaviridae Infections/immunology/pathologyCell DifferentiationGene Expression ProfilingHerpesviridae Infections/immunologyInterleukins/genetics/immunology/metabolismLymphocyte ActivationLymphocytic choriomeningitis virus/immunology/physiologyMiceMice, TransgenicNecrosisReceptors, Interleukin/genetics/metabolismRecombinant Proteins/immunologyRhadinovirus/immunologySignal TransductionStromal Cells/immunology/metabolismT-Lymphocytes, Cytotoxic/immunology/transplantationTumor Virus Infections/immunologyUp-RegulationVaccinia virus/immunologyVirus Replication
PMID: 22323740
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Research groups Infections virales persistantes et maladies autoimmunes (849)
La Sclérose en plaques (908)
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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

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Deposited on : 2013-06-10

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