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Science 292 (5518): 934-937

Copyright © 2001 by the American Association for the Advancement of Science

Vital Involvement of a Natural Killer Cell Activation Receptor in Resistance to Viral Infection

Michael G. Brown,1*dagger Ayotunde O. Dokun,12* Jonathan W. Heusel,1 Hamish R. C. Smith,1 Diana L. Beckman,1 Erika A. Blattenberger,1 Chad E. Dubbelde,1 Laurie R. Stone,1 Anthony A. Scalzo,3 Wayne M. Yokoyama1ddagger

Natural killer (NK) cells are lymphocytes that can be distinguished from T and B cells through their involvement in innate immunity and their lack of rearranged antigen receptors. Although NK cells and their receptors were initially characterized in terms of tumor killing in vitro, we have determined that the NK cell activation receptor, Ly-49H, is critically involved in resistance to murine cytomegalovirus in vivo. Ly-49H requires an immunoreceptor tyrosine-based activation motif (ITAM)-containing transmembrane molecule for expression and signal transduction. Thus, NK cells use receptors functionally resembling ITAM-coupled T and B cell antigen receptors to provide vital innate host defense.

1 Howard Hughes Medical Institute, Rheumatology Division, Washington University School of Medicine, St. Louis, MO 63110, USA.
2 Immunobiology Graduate Program, Mount Sinai School of Medicine, New York, NY 10029, USA.
3 Department of Microbiology, University of Western Australia, Nedlands, Western Australia 6907, Australia.
*   These authors contributed equally to this work.

dagger    Present address: Division of Rheumatology and Immunology, University of Virginia Health Sciences Center, Box 800412, Charlottesville, VA 22908, USA.

ddagger    To whom correspondence should be addressed. E-mail: yokoyama{at}

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Distinct roles of IL-12 and IL-15 in human natural killer cell activation by dendritic cells from secondary lymphoid organs.
G. Ferlazzo, M. Pack, D. Thomas, C. Paludan, D. Schmid, T. Strowig, G. Bougras, W. A. Muller, L. Moretta, and C. Munz (2004)
PNAS 101, 16606-16611
   Abstract »    Full Text »    PDF »
Cmv1-Independent Antiviral Role of NK Cells Revealed in Murine Cytomegalovirus-Infected New Zealand White Mice.
M. Rodriguez, P. Sabastian, P. Clark, and M. G. Brown (2004)
J. Immunol. 173, 6312-6318
   Abstract »    Full Text »    PDF »
NK cell activation by dendritic cells (DCs) requires the formation of a synapse leading to IL-12 polarization in DCs.
C. Borg, A. Jalil, D. Laderach, K. Maruyama, H. Wakasugi, S. Charrier, B. Ryffel, A. Cambi, C. Figdor, W. Vainchenker, et al. (2004)
Blood 104, 3267-3275
   Abstract »    Full Text »    PDF »
Re-Evaluating Natural Resistance to Herpes Simplex Virus Type 1.
W. P. Halford, J. W. Balliet, and B. M. Gebhardt (2004)
J. Virol. 78, 10086-10095
   Abstract »    Full Text »    PDF »
Role of Natural Killer Cells in Innate Protection against Lethal Ebola Virus Infection.
K. L. Warfield, J. G. Perkins, D. L. Swenson, E. M. Deal, C. M. Bosio, M. J. Aman, W. M. Yokoyama, H. A. Young, and S. Bavari (2004)
J. Exp. Med. 200, 169-179
   Abstract »    Full Text »    PDF »
Gain of Virulence Caused by Loss of a Gene in Murine Cytomegalovirus.
I. Bubic, M. Wagner, A. Krmpotic, T. Saulig, S. Kim, W. M. Yokoyama, S. Jonjic, and U. H. Koszinowski (2004)
J. Virol. 78, 7536-7544
   Abstract »    Full Text »    PDF »
NK Cells Stimulate Proliferation of T and NK Cells through 2B4/CD48 Interactions.
E. Assarsson, T. Kambayashi, J. D. Schatzle, S. O. Cramer, A. von Bonin, P. E. Jensen, H.-G. Ljunggren, and B. J. Chambers (2004)
J. Immunol. 173, 174-180
   Abstract »    Full Text »    PDF »
Expansion and Contraction of the NK Cell Compartment in Response to Murine Cytomegalovirus Infection.
S. H. Robbins, M. S. Tessmer, T. Mikayama, and L. Brossay (2004)
J. Immunol. 173, 259-266
   Abstract »    Full Text »    PDF »
Infection of mature monocyte-derived dendritic cells with human cytomegalovirus inhibits stimulation of T-cell proliferation via the release of soluble CD83.
B. Senechal, A. M. Boruchov, J. L. Reagan, D. N. J. Hart, and J. W. Young (2004)
Blood 103, 4207-4215
   Abstract »    Full Text »    PDF »
Toll-like receptors 9 and 3 as essential components of innate immune defense against mouse cytomegalovirus infection.
K. Tabeta, P. Georgel, E. Janssen, X. Du, K. Hoebe, K. Crozat, S. Mudd, L. Shamel, S. Sovath, J. Goode, et al. (2004)
PNAS 101, 3516-3521
   Abstract »    Full Text »    PDF »
Coordinate Expression of Cytokines and Chemokines by NK Cells during Murine Cytomegalovirus Infection.
B. G. Dorner, H. R.C. Smith, A. R. French, S. Kim, J. Poursine-Laurent, D. L. Beckman, J. T. Pingel, R. A. Kroczek, and W. M. Yokoyama (2004)
J. Immunol. 172, 3119-3131
   Abstract »    Full Text »    PDF »

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