|
|
Blood, 1 January 2005, Vol. 105, No. 1, pp. 233-240.
Prepublished online as a Blood First Edition Paper on August 24, 2004; DOI 10.1182/blood-2004-03-1075.
 Previous Article | Next Article 
Submitted March 29, 2004
Accepted August 2, 2004
NKG2D receptor-mediated NK cell function is regulated by inhibitory Ly49 receptors
Jeyarani Regunathan, Yuhong Chen, Demin Wang, and Subramaniam Malarkannan*
Blood Research Institute, Blood Center of Southeastern Wisconsin, Milwaukee, WI, USA
Blood Research Institute, Blood Center of Southeastern Wisconsin, Milwaukee, WI, USA; Department of Microbiology/Molecular Genetics and Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
* Corresponding author; email: smalarkannan{at}bcsew.edu.
Interaction of the activating ligand H60 with NKG2D receptor constitutes a major stimulatory pathway for NK cells. The influence of inhibitory Ly49 receptors on NKG2D-mediated activation is not clearly understood. Here we show that the magnitude of NKG2D-mediated cytotoxicity is directly proportional to both the levels of H60 and the nature of MHC class I molecules expressed on the target cells. The expression levels of H60 on the target cells determined the extent to which the inhibition by Ly49C/I receptors can be overridden. In contrast, even a higher expression of H60 molecule on the target cells failed to overcome the inhibition mediated by Ly49A/G receptors. Also, the level of IFN-gamma and GM-CSF generated by NK cells through anti-NKG2D mAb-mediated activation is significantly reduced by the presence of immobilized anti-Ly49A/G mAbs. Thus, NKG2D-mediated cytotoxicity and cytokine secretion results from the fine balance between activating and inhibitory receptors, and thereby defining the NK cell-mediated immune responses.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
H. Guo, A. Samarakoon, B. Vanhaesebroeck, and S. Malarkannan
The p110{delta} of PI3K plays a critical role in NK cell terminal maturation and cytokine/chemokine generation
J. Exp. Med.,
September 29, 2008;
205(10):
2419 - 2435.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Malarkannan, J. Regunathan, H. Chu, S. Kutlesa, Y. Chen, H. Zeng, R. Wen, and D. Wang
Bcl10 Plays a Divergent Role in NK Cell-Mediated Cytotoxicity and Cytokine Generation
J. Immunol.,
September 15, 2007;
179(6):
3752 - 3762.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Endt, F. E. McCann, C. R. Almeida, D. Urlaub, R. Leung, D. Pende, D. M. Davis, and C. Watzl
Inhibitory Receptor Signals Suppress Ligation-Induced Recruitment of NKG2D to GM1-Rich Membrane Domains at the Human NK Cell Immune Synapse
J. Immunol.,
May 1, 2007;
178(9):
5606 - 5611.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Regunathan, Y. Chen, S. Kutlesa, X. Dai, L. Bai, R. Wen, D. Wang, and S. Malarkannan
Differential and Nonredundant Roles of Phospholipase C{gamma}2 and Phospholipase C{gamma}1 in the Terminal Maturation of NK Cells
J. Immunol.,
October 15, 2006;
177(8):
5365 - 5376.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Nausch, L. Florin, B. Hartenstein, P. Angel, M. Schorpp-Kistner, and A. Cerwenka
Cutting Edge: The AP-1 Subunit JunB Determines NK Cell-Mediated Target Cell Killing by Regulation of the NKG2D-Ligand RAE-1{epsilon}
J. Immunol.,
January 1, 2006;
176(1):
7 - 11.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
