The alarmin interleukin-33 drives protective antiviral CD8⁺ T cell responses.
Bonilla WV., Fröhlich A., Senn K., Kallert S., Fernandez M., Johnson S., Kreutzfeldt M., Hegazy AN., Schrick C., Fallon PG., Klemenz R., Nakae S., Adler H., Merkler D., Löhning M., Pinschewer DD.
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.