Department of Pathology and Immunology, University of Geneva, 1 rue Michel Servet, 1211 Geneva 4, Switzerland.
Science. 2012 Feb 24;335(6071):984-9. doi: 10.1126/science.1215418. Epub 2012 Feb 9.
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.
病原体相关分子模式可显著影响抗病毒免疫反应，而组织损伤的内源性信号（也称为损伤相关分子模式或警报素）的作用仍未明确界定。我们发现，细胞坏死时释放的警报素白细胞介素-33（IL-33）对于复制型 RNA 和 DNA 病毒在小鼠体内引发强烈的 CD8+T 细胞（CTL）反应是必需的。IL-33 通过激活 CTL 上的受体发挥信号作用，以 CTL 内在的方式增强克隆扩增，决定多效性效应细胞分化，并对病毒控制至关重要。此外，重组 IL-33 增强了疫苗诱导的 CTL 反应。脾脏 T 细胞区的放射抗性细胞产生 IL-33，而有效的 CTL 反应需要来自放射抗性细胞而不是造血细胞的 IL-33。因此，放射抗性细胞释放的警报素可协调保护性抗病毒 CTL 反应。
