Dendritic cell-derived IL-15 controls the induction of CD8 T cell immune responses
| Autor: | Ralf Paus, Farhad Mirghomizadeh, René Rückert, Katja Brandt, Elena Bulanova, Silvia Bulfone-Paus |
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| Rok vydání: | 2003 |
| Předmět: |
T cell
Immunology CD8-Positive T-Lymphocytes Biology Dermatitis Contact Lymphocyte Activation Mice Immune system medicine Animals Immunology and Allergy Cytotoxic T cell Hypersensitivity Delayed Autocrine signalling B cell Interleukin-15 Receptors Interleukin-15 Tumor Necrosis Factor-alpha Receptors Interleukin-2 Dendritic Cells Dendritic cell Molecular biology Interleukin-10 Mice Inbred C57BL medicine.anatomical_structure Interleukin 15 Antibody Formation Interleukin-2 CD8 Interleukin-1 |
| Zdroj: | European Journal of Immunology. 33:3493-3503 |
| ISSN: | 1521-4141 0014-2980 |
| DOI: | 10.1002/eji.200324545 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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