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The Journal of Immunology, 2007, 178: 4764-4770.
Copyright © 2007 by The American Association of Immunologists, Inc.

NK Cell Maturation and Peripheral Homeostasis Is Associated with KLRG1 Up-Regulation1

Nicholas D. Huntington2,3,*,{dagger}, Hy Tabarias§, Kirsten Fairfax*,{dagger}, Jason Brady*, Yoshihiro Hayakawa{ddagger}, Mariapia A. Degli-Esposti§, Mark J. Smyth{ddagger}, David M. Tarlinton* and Stephen L. Nutt*

* Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; {dagger} Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia; {ddagger} Cancer Immunology Program, Sir Donald and Lady Trescowick Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia; § Centre for Experimental Immunology, Lions Eye Institute, Nedlands, West Australia, Australia; and Immunology and Virology Program, Centre for Ophthalmology and Visual Science, University of Western Australia, Western Australia, Australia

NK cells are important for the clearance of tumors, parasites, and virus-infected cells. Thus, factors that control NK cell numbers and function are critical for the innate immune response. A subset of NK cells express the inhibitory killer cell lectin-like receptor G1 (KLRG1). In this study, we identify that KLRG1 expression is acquired during periods of NK cell division such as development and homeostatic proliferation. KLRG1+ NK cells are mature in phenotype, and we show for the first time that these cells have a slower in vivo turnover rate, reduced proliferative response to IL-15, and poorer homeostatic expansion potential compared with mature NK cells lacking KLRG1. Transfer into lymphopenic recipients indicate that KLRG1 NK cells are precursors of KLRG1+ NK cells and KLRG1 expression accumulates following cell division. Furthermore, KLRG1+ NK cells represent a significantly greater proportion of NK cells in mice with enhanced NK cell numbers such as Cd45–/– mice. These data indicate that NK cells acquire KLRG1 on their surface during development, and this expression correlates with functional distinctions from other peripheral NK cells in vivo.

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 was supported by Cancer Council Victoria Sydney Parker Smith Postdoctoral Cancer Research Fellowship (to N.D.H.), National Health and Medical Research Council of Australia, and Walter and Eliza Hall of Medical Research Metcalf Fellowship (to S.L.N.).

2 Current address: Cytokine and Lymphoid Development Unit, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris, France.

3 Address correspondence and reprint requests to Dr. Nicholas D. Huntington, Institut Pasteur, Cytokine and Lymphoid Development, 25 rue du Docteur Roux, 75724 Paris, France. E-mail address: nhunting{at}pasteur.fr

4 Abbreviations used in this paper: Imm, immature; BM, bone marrow; KLRG1, killer cell lectin-like receptor G1; MCMV, murine CMV; PI, propidium iodide; M1, mature 1; M2, mature 2.




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