NDLI: Inhibition of tumor growth by NK1.1+ cells and CD8+ T cells activated by IL-15 through receptor beta/common gamma signaling in trans.

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Inhibition of tumor growth by NK1.1+ cells and CD8+ T cells activated by IL-15 through receptor beta/common gamma signaling in trans.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Wu, T-C Monie, Archana Rowley, Jesse Hung, Chien-Fu
Description	Country affiliation: United States Author Affiliation: Rowley J ( Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.)
Abstract	IL-15 is an important cytokine involved in the survival and function of CD8(+) T cells and NK cells. IL-15 can be presented by IL-15Ralpha (IL-15RA) to bind with the shared IL-2/IL-15Rbeta and common gamma-chains, which activate signaling pathways on NK cells and CD8(+) T cells. In the present study, we characterized the function of trans-presented IL-15 on NK cells and CD8(+) T cells using TC-1 tumor cells transduced with a retrovirus encoding IL-15 linked to IL-15RA (IL-15/IL-15RA). We demonstrated that the expression of IL-15/IL-15RA on TC-1 cells led to increased percentages of tumor-infiltrating NK cells, NKT cells, and CD8(+) T cells, resulting in the inhibition of tumor growth in challenged mice. Additionally, in vivo Ab depletion experiments demonstrated that NK1.1(+) cells and CD8(+) T cells were important in this inhibition of tumor growth. Furthermore, this accumulation of immune cells and inhibition of tumor growth was abolished by a single amino acid mutation in the common gamma-chain binding site on IL-15. We also observed that IL-15/IL-15RA-transduced TC-1 cells led to the activation of STAT5 in NK and CD8(+) T cells in trans, which was abolished in the mutated IL-15/IL-15RA-transduced TC-1 cells. Taken together, our data suggest that common gamma-chain binding-dependent activation of the shared IL-15/IL-2Rbeta/common gamma signaling pathway may play an important role in the activation of NK cells and CD8(+) T cells, resulting in IL-15/IL-15RA trans-presentation-mediated inhibition of tumor growth.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	12
Volume Number	181
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2008-12-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Antigens, Ly Biosynthesis Cd8-positive T-lymphocytes Immunology Growth Inhibitors Physiology Interleukin Receptor Common Gamma Subunit Interleukin-15 Interleukin-2 Receptor Beta Subunit Killer Cells, Natural Nk Cell Lectin-like Receptor Subfamily B Ovarian Neoplasms Prevention & Control Signal Transduction Animals Antigen Presentation Genetics Metabolism Pathology Cell Line, Tumor Interleukin-15 Receptor Alpha Subunit Lymphocyte Activation Mice Mice, Inbred C57bl Mice, Transgenic Virology Retroviridae Transduction, Genetic Research Support, N.i.h., Extramural Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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