Dendritic cell‐derived IL‐15 controls the induction of CD8 T cell immune responses

<jats:title>Abstract</jats:title><jats:p>The development and the differentiation of CD8<jats:sup>+</jats:sup> T cells are dependent on IL‐15. Here, we have studied the source and mechanism of how IL‐15 modulates CD8<jats:sup>+</jats:sup> T cell‐mediated Th1immune responses by employing two delayed‐type hypersensitivity (DTH) models. IL‐15‐deficient (IL‐15<jats:sup>–/–</jats:sup>) mice or mice treated with soluble IL‐15Rα as an IL‐15 antagonist showed significantly reduced CD8<jats:sup>+</jats:sup> T cell‐dependent DTH responses, while activation of CD4<jats:sup>+</jats:sup> T cell and B cell functions remained unaffected. Injection of antigen‐labeled dendritic cells (DC) fromIL‐15<jats:sup>+/+</jats:sup>, IL‐15<jats:sup>–/–</jats:sup> or IL‐15Rα<jats:sup>–/–</jats:sup> mice revealed that DC‐derived IL‐15 is an absolute requirement for the initiation of DTH response. The re‐establishment of the interaction of IL‐15 with the IL‐15Rα by incubating IL‐15<jats:sup>–/–</jats:sup> DC with IL‐15 completely restored the capacity to prime T cells for DTH induction <jats:italic>in vivo</jats:italic>. Moreover, IL‐15 also enhanced secretion of pro‐inflammatory cytokines by DC and triggered <jats:italic>in vitro</jats:italic> CD8<jats:sup>+</jats:sup> T cell proliferation and IL‐2 release. Taken together, the data suggest that an autocrine IL‐15/IL‐15Rα signaling loop in DC is essential for inducing CD8<jats:sup>+</jats:sup>‐dependent Th1 immune responses in mice. Therefore, targeted manipulation of this loop promises to be an effective, novel strategy for therapeuticmodulation of clinically relevant DTH reactions.</jats:p>