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Published online September 28, 2009
The Journal of Immunology, 2009, 183, 4948 -4956
Copyright © 2009 by The American Association of Immunologists, Inc.
doi:10.4049/jimmunol.0900719
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Dendritic Cells Support the In Vivo Development and Maintenance of NK Cells via IL-15 Trans-Presentation1

Eliseo F. Castillo, Spencer W. Stonier, Loredana Frasca,2 and Kimberly S. Schluns3

Department of Immunology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030

IL-15 is a key component that regulates the development and homeostasis of NK cells and is delivered through a mechanism termed trans-presentation. During development, multiple events must proceed to generate a functional mature population of NK cells that are vital for tumor and viral immunity. Nevertheless, how IL-15 regulates these various events and more importantly what cells provide IL-15 to NK cells to drive these events is unclear. It is known dendritic cells (DC) can activate NK cells via IL-15 trans-presentation; however, the ability of DC to use IL-15 trans-presentation to promote the development and homeostatic maintenance of NK cell has not been established. In this current study, we show that IL-15 trans-presentation solely by CD11c+ cells assists the in vivo development and maintenance of NK cells. More specifically, DC-mediated IL-15 trans-presentation drove the differentiation of NK cells, which included the up-regulation of the activating and inhibitory Ly49 receptors. Although these cells did not harbor a mature CD11bhigh phenotype, they were capable of degranulating and producing IFN-{gamma} upon stimulation similar to wild-type NK cells. In addition, DC facilitated the survival of mature NK cells via IL-15 trans-presentation in the periphery. Thus, an additional role for NK-DC interactions has been identified whereby DC support the developmental and homeostatic niche of NK cells.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 This work is supported by National Institutes of Health Grant AI070910 and the M.D. Anderson Trust Fellowship (to K.S.).

2 Current address: Department of Infectious, Parasitic, and Immune-Mediated Diseases, Anti-Infectious Immunity Unit, Istituto Superiore di Sanità, Rome, Italy.

3 Address correspondence and reprint request to Dr. Kimberly S. Schluns, Department of Immunology, M/C 901, University of Texas M.D. Anderson Cancer Center, P.O. Box 301429, Houston, TX 77030. E-mail address: kschluns{at}mdanderson.org

4 Abbreviations used in this paper: NKp, NK precursor; BM, bone marrow; DC, dendritic cell; Tg, transgenic; Wt, wild type.






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