High dose CD11c-driven IL15 is sufficient to drive NK cell maturation and anti-tumor activity in a trans-presentation independent manner

The common gamma (?c)-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 a (Ra)-chain. We have identified distinct effects on selected IL15-responsive populations. While CD8+ T cells required complexed forms of IL15/IL15Ra for full functionality, mature NK populations were rescued in an IL15/IL15Ra-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 Ra-complex as a powerful and specific immuno-modulator, which may be beneficial where selective immune-activation is desired.

• Autores: Polansky J.K.; Bahri R.; Divivier M.; Duitman E.H.; Vock C.; Goyeneche Patiño, Diego Andres; Orinska Z.; Bulfone-Paus S.
• Tipo de recurso: Article of journal
• Fecha de publicación: 2016
• Institución: Universidad Cooperativa de Colombia
• Repositorio: Repositorio UCC
• OAI Identifier: oai:repository.ucc.edu.co:20.500.12494/41677
• Acceso en línea: https://doi.org/10.14295/bds.2020.v23i3.2055; https://hemeroteca.unad.edu.co/index.php/riaa/article/view/2067; https://hdl.handle.net/20.500.12494/41677
• Palabra clave: glycoprotein p 15095; Il15ra protein; mouse; interleukin 15; interleukin 15 receptor; animal; antigen presentation; CD8+ T lymphocyte; cell differentiation; cytology; cytotoxicity; experimental melanoma; genetics; immunology; knockout mouse; metabolism; metastasis; mouse; natural killer cell; neoplasm; pathology; Peyer patch; physiology; promoter region; thymus; transgenic mouse; tumor cell line; Animals; Antigen Presentation; Antigens; CD11c; CD8-Positive T-Lymphocytes; Cell Differentiation; Cell Line; Tumor; Cytotoxicity; Immunologic; Interleukin-15; Killer Cells; Natural; Melanoma; Experimental; Mice; Mice; Knockout; Mice; Transgenic; Neoplasm Metastasis; Neoplasms; Peyer's Patches; Promoter Regions; Genetic; Receptors; Interleukin-15; Thymus Gland
• Rights: closedAccess
• License: http://purl.org/coar/access_right/c_14cb