Preassociation of IL-15 with IL-15R alpha-IgG1-Fc enhances its activity on proliferation of NK and CD8+/CD44high T cells and its antitumor action
| Autor: | Thomas A. Waldmann, Jiirgen R. Müller, Hiral J. Patel, Sigrid Dubois, Meili Zhang |
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| Rok vydání: | 2008 |
| Předmět: |
Recombinant Fusion Proteins
Immunology Molecular Sequence Data Melanoma Experimental Antineoplastic Agents Biology CD8-Positive T-Lymphocytes Cell Line Interleukin 21 Mice Immune system Interleukin-15 Receptor alpha Subunit In vivo T-Lymphocyte Subsets Immunology and Allergy Cytotoxic T cell Animals Humans Amino Acid Sequence Cells Cultured Cell Proliferation Interleukin-15 Mice Knockout Molecular biology In vitro Immunoglobulin Fc Fragments Up-Regulation Killer Cells Natural Mice Inbred C57BL Hyaluronan Receptors Interleukin 15 Cell culture Immunoglobulin G Female CD8 |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 180(4) |
| ISSN: | 0022-1767 |
| Popis: | In the induction of an immune response, IL-15Rα on APCs transpresents IL-15 to NK and CD8+/CD44high T cells that express the IL-2/15Rβ and γc subunits only. In this study, we show data mimicking this transpresentation by using IL-15 preassociated with a chimeric protein that is comprised of the extracellular domain of murine IL-15Rα and the Fc portion of human IgG1. When tested in vitro, IL-15Rα-IgG1-Fc strongly increased the IL-15-mediated proliferation of murine NK and CD8+/CD44high T cells. The effect of IL-15Rα-IgG1-Fc was dependent on the presence of both IgG1-Fc and IL-15Rα. When injected into mice, IL-15Rα-IgG1-Fc enhanced the capacity of IL-15 to expand the number of NK and CD8+/CD44high T cells. The effect on cell numbers in vivo also depended on Fc receptor binding because reduced expansion was observed in FcRγ−/− mice. NK cells cultured in IL-15/IL-15Rα-IgG1-Fc complex gained cytotoxic activity toward a number of NK-sensitive targets. When mice bearing the NK-sensitive syngeneic tumor B16 were treated, the presence of IL-15Rα-IgG1-Fc increased the antitumor activity of IL-15. Thus, a preassociation with IL-15Rα-IgG1-Fc enhances the activities of IL-15 in vivo and in vitro that may be useful in the treatment of tumors. |
| Databáze: | OpenAIRE |
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