rdf:type |
|
lifeskim:mentions |
umls-concept:C0039194,
umls-concept:C0085358,
umls-concept:C0254610,
umls-concept:C0441472,
umls-concept:C0441655,
umls-concept:C1149192,
umls-concept:C1332717,
umls-concept:C1413244,
umls-concept:C1514485,
umls-concept:C1706438,
umls-concept:C2349975,
umls-concept:C2698600
|
pubmed:issue |
4
|
pubmed:dateCreated |
2008-2-5
|
pubmed:abstractText |
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.
|
pubmed:language |
eng
|
pubmed:journal |
|
pubmed:citationSubset |
AIM
|
pubmed:chemical |
|
pubmed:status |
MEDLINE
|
pubmed:month |
Feb
|
pubmed:issn |
0022-1767
|
pubmed:author |
|
pubmed:issnType |
Print
|
pubmed:day |
15
|
pubmed:volume |
180
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
2099-106
|
pubmed:meshHeading |
pubmed-meshheading:18250415-Amino Acid Sequence,
pubmed-meshheading:18250415-Animals,
pubmed-meshheading:18250415-Antigens, CD44,
pubmed-meshheading:18250415-Antineoplastic Agents,
pubmed-meshheading:18250415-CD8-Positive T-Lymphocytes,
pubmed-meshheading:18250415-Cell Line,
pubmed-meshheading:18250415-Cell Proliferation,
pubmed-meshheading:18250415-Cells, Cultured,
pubmed-meshheading:18250415-Female,
pubmed-meshheading:18250415-Humans,
pubmed-meshheading:18250415-Immunoglobulin Fc Fragments,
pubmed-meshheading:18250415-Immunoglobulin G,
pubmed-meshheading:18250415-Interleukin-15,
pubmed-meshheading:18250415-Interleukin-15 Receptor alpha Subunit,
pubmed-meshheading:18250415-Killer Cells, Natural,
pubmed-meshheading:18250415-Melanoma, Experimental,
pubmed-meshheading:18250415-Mice,
pubmed-meshheading:18250415-Mice, Inbred C57BL,
pubmed-meshheading:18250415-Mice, Knockout,
pubmed-meshheading:18250415-Molecular Sequence Data,
pubmed-meshheading:18250415-Recombinant Fusion Proteins,
pubmed-meshheading:18250415-T-Lymphocyte Subsets,
pubmed-meshheading:18250415-Up-Regulation
|
pubmed:year |
2008
|
pubmed:articleTitle |
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.
|
pubmed:affiliation |
Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA.
|
pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Intramural
|