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Using a new series of transgenic mice, we analyzed the <jats:italic>in vivo<\/jats:italic> 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 \u03b1 (R\u03b1)-chain. We have identified distinct effects on selected IL15-responsive populations. While CD8<jats:sup>+<\/jats:sup> T cells required complexed forms of IL15\/IL15R\u03b1 for full functionality, mature NK populations were rescued in an IL15\/IL15R\u03b1-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 \u201cfree\u201d IL15 in the absence of R\u03b1-complex as a powerful and specific immuno-modulator, which may be beneficial where selective immune-activation is desired.<\/jats:p>","DOI":"10.1038\/srep19699","type":"journal-article","created":{"date-parts":[[2016,1,29]],"date-time":"2016-01-29T10:41:31Z","timestamp":1454064091000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["High dose CD11c-driven IL15 is sufficient to drive NK cell maturation and anti-tumor activity in a trans-presentation independent manner"],"prefix":"10.1038","volume":"6","author":[{"given":"Julia K.","family":"Polansky","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajia","family":"Bahri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mylene","family":"Divivier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erwin H.","family":"Duitman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Vock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego A.","family":"Goyeneche-Patino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zane","family":"Orinska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Bulfone-Paus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,1,29]]},"reference":[{"key":"BFsrep19699_CR1","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1084\/jem.191.5.771","volume":"191","author":"MK Kennedy","year":"2000","unstructured":"Kennedy, M. 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