title: Dendritic cell-derived IL-15 controls the induction of CD8 T cell immune responses.
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-15Ralpha 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-15Ralpha(-/-) 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-15Ralpha 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 pro-inflammatory 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-15Ralpha 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.
authors.affiliation: Research Center Borstel, Department of Immunology and Cell Biology, Borstel, Germany.
authors.forename: René
authors.initials: R
authors.lastname: Rückert
authors.forename: Katja
authors.initials: K
authors.lastname: Brandt
authors.forename: Elena
authors.initials: E
authors.lastname: Bulanova
authors.forename: Farhad
authors.initials: F
authors.lastname: Mirghomizadeh
authors.forename: Ralf
authors.initials: R
authors.lastname: Paus
authors.forename: Silvia
authors.initials: S
authors.lastname: Bulfone-Paus
mesh_terms: D000818:Animals; D000917:Antibody Formation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000502:physiology*; D003877:Dermatitis, Contact / Q000209:etiology; D006968:Hypersensitivity, Delayed / Q000209:etiology; D007375:Interleukin-1 / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D019409:Interleukin-15 / Q000502:physiology*; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: C508025:Il15ra protein, mouse; D007375:Interleukin-1; D019409:Interleukin-15; D007376:Interleukin-2; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10