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

Publication Date

24/02/2012

Volume

335

Pages

984 - 989

Keywords

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