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Published online July 31, 2009
The Journal of Immunology, 2009, 183, 2911 -2914
Copyright © 2009 by The American Association of Immunologists, Inc.
doi:10.4049/jimmunol.0901872

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Cutting Edge: IL-15-Independent NK Cell Response to Mouse Cytomegalovirus Infection1

Joseph C. Sun*, Averil Ma{dagger} and Lewis L. Lanier2,*

* Department of Microbiology and Immunology and the Cancer Research Institute and {dagger} Department of Medicine, University of California, San Francisco, CA 94143

NK cells respond rapidly during viral infection. The development, function, and survival of NK cells are thought to be dependent on IL-15. In mice lacking IL-15, NK cells are found in severely decreased numbers. Surprisingly, following infection of IL-15- and IL-15R{alpha}-deficient mice with mouse CMV, we measured a robust proliferation of Ly49H-bearing NK cells in lymphoid and nonlymphoid organs capable of cytokine secretion and cytolytic function. Remarkably, even in Rag2–/– x Il2rg–/– mice, a widely used model of NK cell deficiency, we detected a significant number of NK cells 1 wk after mouse CMV infection. In these mice we measured a >300-fold expansion of NK cells, which was dependent on recognition of the m157 viral glycoprotein ligand and IL-12. Together, these findings demonstrate a previously unrecognized independence of NK cells on IL-15 or other common {gamma} signaling cytokines during their response against viral infection.

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 study was supported by National Institutes of Health Grant AI068129. L.L.L. is an American Cancer Society Professor. J.C.S. is an Irvington Postdoctoral Fellow of the Cancer Research Institute.

2 Address correspondence and reprint requests to Dr. Lewis L. Lanier, University of California, San Francisco, Department of Microbiology and Immunology, 513 Parnassus Avenue, Room HSE-1001G, Box 0414, San Francisco, CA 94143-0414. E-mail address: Lewis.Lanier{at}ucsf.edu

3 Abbreviations used in this paper MCMV, mouse cytomegalovirus; {gamma}C, IL-2R common {gamma}-chain; LAMP, lysosome-associated membrane protein; PI, postinfection; WT, wild type.

4 The online version of this article contains supplemental material.







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