Dendritic cell-derived IL-15 controls the induction of CD8 T cell immune reponses

René Rückert, Katja Brandt, Elena Bulanova, Farhad Mirghomizadeh, Ralf Paus, Silvia Bulfone-Paus

Research output: Contribution to journalArticlepeer-review

75 Scopus citations

Abstract

The development and the differentiation of CD8+ T cells are dependent on IL-15. Here, we have studied the source and mechanism of how IL-15 modulates CD8+ T cell-mediated Th1 immune responses by employing two delayed-type hypersensitivity (DTH) models. IL-15-deficient (IL-15-/-) mice or mice treated with soluble IL-15Rα as an IL-15 antagonist showed significantly reduced CD8+ T cell-dependent DTH responses, while activation of CD4+ T cell and B cell functions remained unaffected. Injection of antigen-labeled dendritic cells (DC) from IL-15+/+, IL-15-/- or IL-15Rα-/- 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-/- DC with IL-15 completely restored the capacity to prime T cells for DTH induction in vivo. Moreover, IL-15 also enhanced secretion of proinflammatory cytokines by DC and triggered in vitro CD8+ 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+-dependent Th1 immune responses in mice. Therefore, targeted manipulation of this loop promises to be an effective, novel strategy for therapeutic modulation of clinically relevant DTH reactions.

Original languageEnglish (US)
Pages (from-to)3493-3503
Number of pages11
JournalEuropean Journal of Immunology
Volume33
Issue number12
DOIs
StatePublished - Dec 1 2003
Externally publishedYes

Keywords

  • Cytokines
  • Dendritic cells
  • Inflammation
  • Rodent

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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