title: High dose CD11c-driven IL15 is sufficient to drive NK cell maturation and anti-tumor activity in a trans-presentation independent manner.
abstract: The common gamma (γc)-chain cytokine interleukin 15 (IL15) is a multifunctional immune-modulator which impacts the generation, maturation and activity of many cell types of the innate, as well as the adaptive immune system, including natural killer (NK) and CD8(+) T cells. Using a new series of transgenic mice, we analyzed the in vivo potential of IL15 as an immune-regulator when available at different concentrations or delivery modes, i.e. soluble monomer or complexed to its specific receptor α (Rα)-chain. We have identified distinct effects on selected IL15-responsive populations. While CD8(+) T cells required complexed forms of IL15/IL15Rα for full functionality, mature NK populations were rescued in an IL15/IL15Rα-deficient environment by high levels of CD11c-restricted IL15. These IL15-conditions were sufficient to limit tumor formation in a lung metastasis model indicating that the NK cell populations were fully functional. These data underline the potential of "free" IL15 in the absence of Rα-complex as a powerful and specific immuno-modulator, which may be beneficial where selective immune-activation is desired.
authors.affiliation: Research Center Borstel, 23845 Borstel, Germany.
authors.forename: Julia K
authors.initials: JK
authors.lastname: Polansky
authors.affiliation: Research Center Borstel, 23845 Borstel, Germany.|Institute of Inflammation and Repair &MCCIR, University of Manchester, Manchester M13 9PT, UK.
authors.forename: Rajia
authors.initials: R
authors.lastname: Bahri
authors.affiliation: Research Center Borstel, 23845 Borstel, Germany.
authors.forename: Mylene
authors.initials: M
authors.lastname: Divivier
authors.affiliation: Research Center Borstel, 23845 Borstel, Germany.
authors.forename: Erwin H
authors.initials: EH
authors.lastname: Duitman
authors.affiliation: Research Center Borstel, 23845 Borstel, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Vock
authors.affiliation: Facultad de Medicina Veterinaria y Zootecnia, Universidad Cooperativa de Colombia, Bucaramanga, Colombia.
authors.forename: Diego A
authors.initials: DA
authors.lastname: Goyeneche-Patino
authors.affiliation: Research Center Borstel, 23845 Borstel, Germany.
authors.forename: Zane
authors.initials: Z
authors.lastname: Orinska
authors.affiliation: Institute of Inflammation and Repair &MCCIR, University of Manchester, Manchester M13 9PT, UK.
authors.forename: Silvia
authors.initials: S
authors.lastname: Bulfone-Paus
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D039521:CD11c Antigen / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D019409:Interleukin-15 / Q000235:genetics / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000166:cytology / Q000502:physiology*; D008546:Melanoma, Experimental; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010581:Peyer's Patches / Q000166:cytology / Q000276:immunology; D011401:Promoter Regions, Genetic; D053647:Receptors, Interleukin-15 / Q000235:genetics; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
chemical_list: D039521:CD11c Antigen; C508025:Il15ra protein, mouse; D019409:Interleukin-15; D053647:Receptors, Interleukin-15
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