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.

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. Research Abstract Details 

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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. Abstract Text:

Sigrid Dubois,Hiral J Patel,Meili Zhang,Thomas A Waldmann,Jürgen R Müller,

In the induction of an immune response, IL-15Ralpha on APCs transpresents IL-15 to NK and CD8(+)/CD44(high) T cells that express the IL-2/15Rbeta and gammac 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-15Ralpha and the Fc portion of human IgG1. When tested in vitro, IL-15Ralpha-IgG1-Fc strongly increased the IL-15-mediated proliferation of murine NK and CD8(+)/CD44(high) T cells. The effect of IL-15Ralpha-IgG1-Fc was dependent on the presence of both IgG1-Fc and IL-15Ralpha. When injected into mice, IL-15Ralpha-IgG1-Fc enhanced the capacity of IL-15 to expand the number of NK and CD8(+)/CD44(high) T cells. The effect on cell numbers in vivo also depended on Fc receptor binding because reduced expansion was observed in FcRgamma(-/-) mice. NK cells cultured in IL-15/IL-15Ralpha-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-15Ralpha-IgG1-Fc increased the antitumor activity of IL-15. Thus, a preassociation with IL-15Ralpha-IgG1-Fc enhances the activities of IL-15 in vivo and in vitro that may be useful in the treatment of tumors.

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. Publishing Authors By Initials

S Dubois,HJ Patel,M Zhang,TA Waldmann,JR Müller,

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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. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Journal of immunology (Baltimore, Md. : 1950)

VOLUME: 180

Page Numbers: 2099-106

Journal Abbreviation: J. Immunol.

ISSN: 0022-1767

DAY: 15

MONTH: Feb

YEAR: 2008

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. Information

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LANGUAGE: eng

NlmUniqueID: 2985117

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Grant and Affiliation Information for 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.

AFFILIATION: Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.

Country: United States

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MEDLINETA: J Immunol

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