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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.

Original publication

DOI

10.1126/science.1215418

Type

Journal article

Journal

Science (New York, N.Y.)

Publication Date

09/02/2012

Volume

335

Pages

984 - 989

Addresses

Department of Pathology and Immunology, University of Geneva, 1 rue Michel Servet, 1211 Geneva 4, Switzerland.

Keywords

T-Lymphocytes, Cytotoxic, Stromal Cells, Animals, Mice, Transgenic, Mice, Rhadinovirus, Vaccinia virus, Lymphocytic choriomeningitis virus, Herpesviridae Infections, Arenaviridae Infections, Tumor Virus Infections, Necrosis, Receptors, Interleukin, Recombinant Proteins, Interleukins, Adoptive Transfer, Gene Expression Profiling, Lymphocyte Activation, Virus Replication, Signal Transduction, Cell Differentiation, Up-Regulation, Interleukin-33, Interleukin-1 Receptor-Like 1 Protein