HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wiemann, K. Articles by Steinle, A. Search for Related Content PubMed PubMed Citation Articles by Wiemann, K. Articles by Steinle, A.

Systemic NKG2D Down-Regulation Impairs NK and CD8 T Cell Responses In Vivo¹

Katrin Wiemann^*, Hans-Willi Mittrücker, Ute Feger^*, Stefan A. Welte^*, Wayne M. Yokoyama, Thomas Spies, Hans-Georg Rammensee^* and Alexander Steinle^2,*

^* Department of Immunology, Institute for Cell Biology, Eberhard Karls University Tübingen, Tübingen, Germany; Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany; Howard Hughes Medical Institute, Division of Rheumatology, Washington University School of Medicine and Barnes-Jewish Hospital, St. Louis, MO 63110; and Fred Hutchinson Cancer Research Center, Clinical Research Division, Seattle, WA 98109

The immunoreceptor NKG2D stimulates activation of cytotoxic lymphocytes upon engagement with MHC class I-related NKG2D ligands of which at least some are expressed inducibly upon exposure to carcinogens, cell stress, or viruses. In this study, we investigated consequences of a persistent NKG2D ligand expression in vivo by using transgenic mice expressing MHC class I chain-related protein A (MICA) under control of the H2-K^b promoter. Although MICA functions as a potent activating ligand of mouse NKG2D, H2-K^b-MICA mice appear healthy without aberrations in lymphocyte subsets. However, NKG2D-mediated cytotoxicity of H2-K^b-MICA NK cells is severely impaired in vitro and in vivo. This deficiency concurs with a pronounced down-regulation of surface NKG2D that is also seen on activated CD8 T cells. As a consequence, H2-K^b-MICA mice fail to reject MICA-expressing tumors and to mount normal CD8 T cell responses upon Listeria infection emphasizing the importance of NKG2D in immunity against tumors and intracellular infectious agents.

This article has been cited by other articles:

				P. Roda-Navarro and H. T. Reyburn The Traffic of the NKG2D/Dap10 Receptor Complex during Natural Killer (NK) Cell Activation J. Biol. Chem., June 12, 2009; 284(24): 16463 - 16472. [Abstract] [Full Text] [PDF]

				C. Cerboni, M. Ardolino, A. Santoni, and A. Zingoni Detuning CD8+ T lymphocytes by down-regulation of the activating receptor NKG2D: role of NKG2D ligands released by activated T cells Blood, March 26, 2009; 113(13): 2955 - 2964. [Abstract] [Full Text] [PDF]

				R. Apps, L. Gardner, J. Traherne, V. Male, and A. Moffett Natural-killer cell ligands at the maternal-fetal interface: UL-16 binding proteins, MHC class-I chain related molecules, HLA-F and CD48 Hum. Reprod., November 1, 2008; 23(11): 2535 - 2548. [Abstract] [Full Text] [PDF]

				S. K. Tripathy, P. A. Keyel, L. Yang, J. T. Pingel, T. P. Cheng, A. Schneeberger, and W. M. Yokoyama Continuous engagement of a self-specific activation receptor induces NK cell tolerance J. Exp. Med., August 4, 2008; 205(8): 1829 - 1841. [Abstract] [Full Text] [PDF]

				I. Waldhauer, D. Goehlsdorf, F. Gieseke, T. Weinschenk, M. Wittenbrink, A. Ludwig, S. Stevanovic, H.-G. Rammensee, and A. Steinle Tumor-Associated MICA Is Shed by ADAM Proteases Cancer Res., August 1, 2008; 68(15): 6368 - 6376. [Abstract] [Full Text] [PDF]

				D. R. Siemens, N. Hu, A. K. Sheikhi, E. Chung, L. J. Frederiksen, H. Pross, and C. H. Graham Hypoxia Increases Tumor Cell Shedding of MHC Class I Chain-Related Molecule: Role of Nitric Oxide Cancer Res., June 15, 2008; 68(12): 4746 - 4753. [Abstract] [Full Text] [PDF]

				A. Clayton, J. P. Mitchell, J. Court, S. Linnane, M. D. Mason, and Z. Tabi Human Tumor-Derived Exosomes Down-Modulate NKG2D Expression J. Immunol., June 1, 2008; 180(11): 7249 - 7258. [Abstract] [Full Text] [PDF]

				J. D. Coudert, L. Scarpellino, F. Gros, E. Vivier, and W. Held Sustained NKG2D engagement induces cross-tolerance of multiple distinct NK cell activation pathways Blood, April 1, 2008; 111(7): 3571 - 3578. [Abstract] [Full Text] [PDF]

				S. Diermayr, H. Himmelreich, B. Durovic, A. Mathys-Schneeberger, U. Siegler, U. Langenkamp, J. Hofsteenge, A. Gratwohl, A. Tichelli, M. Paluszewska, et al. NKG2D ligand expression in AML increases in response to HDAC inhibitor valproic acid and contributes to allorecognition by NK-cell lines with single KIR-HLA class I specificities Blood, February 1, 2008; 111(3): 1428 - 1436. [Abstract] [Full Text] [PDF]

				Y.-J. Kim, M.-K. Han, and H. E. Broxmeyer 4-1BB regulates NKG2D costimulation in human cord blood CD8+ T cells Blood, February 1, 2008; 111(3): 1378 - 1386. [Abstract] [Full Text] [PDF]

				A. I. Marusina, S. J. Burgess, I. Pathmanathan, F. Borrego, and J. E. Coligan Regulation of Human DAP10 Gene Expression in NK and T Cells by Ap-1 Transcription Factors J. Immunol., January 1, 2008; 180(1): 409 - 417. [Abstract] [Full Text] [PDF]

				L. Elsner, V. Muppala, M. Gehrmann, J. Lozano, D. Malzahn, H. Bickeboller, E. Brunner, M. Zientkowska, T. Herrmann, L. Walter, et al. The Heat Shock Protein HSP70 Promotes Mouse NK Cell Activity against Tumors That Express Inducible NKG2D Ligands J. Immunol., October 15, 2007; 179(8): 5523 - 5533. [Abstract] [Full Text] [PDF]

				H. Zhang, K. M. Snyder, M. M. Suhoski, M. V. Maus, V. Kapoor, C. H. June, and C. L. Mackall 4-1BB Is Superior to CD28 Costimulation for Generating CD8+ Cytotoxic Lymphocytes for Adoptive Immunotherapy J. Immunol., October 1, 2007; 179(7): 4910 - 4918. [Abstract] [Full Text] [PDF]

				F. E. McCann, P. Eissmann, B. Onfelt, R. Leung, and D. M. Davis The Activating NKG2D Ligand MHC Class I-Related Chain A Transfers from Target Cells to NK Cells in a Manner That Allows Functional Consequences J. Immunol., March 15, 2007; 178(6): 3418 - 3426. [Abstract] [Full Text] [PDF]

				P. Roda-Navarro, M. Vales-Gomez, S. E. Chisholm, and H. T. Reyburn Transfer of NKG2D and MICB at the cytotoxic NK cell immune synapse correlates with a reduction in NK cell cytotoxic function PNAS, July 25, 2006; 103(30): 11258 - 11263. [Abstract] [Full Text] [PDF]

				M. Jinushi, F. S. Hodi, and G. Dranoff Therapy-induced antibodies to MHC class I chain-related protein A antagonize immune suppression and stimulate antitumor cytotoxicity PNAS, June 13, 2006; 103(24): 9190 - 9195. [Abstract] [Full Text] [PDF]

				M. T. Borchers, N. L. Harris, S. C. Wesselkamper, S. Zhang, Y. Chen, L. Young, and G. W. Lau The NKG2D-Activating Receptor Mediates Pulmonary Clearance of Pseudomonas aeruginosa. Infect. Immun., May 1, 2006; 74(5): 2578 - 2586. [Abstract] [Full Text] [PDF]

				S. J. Burgess, A. I. Marusina, I. Pathmanathan, F. Borrego, and J. E. Coligan IL-21 Down-Regulates NKG2D/DAP10 Expression on Human NK and CD8+ T Cells J. Immunol., February 1, 2006; 176(3): 1490 - 1497. [Abstract] [Full Text] [PDF]