Systemic NKG2D down-regulation impairs NK and CD8 T cell responses in vivo |
| |
Authors: | Wiemann Katrin Mittrücker Hans-Willi Feger Ute Welte Stefan A Yokoyama Wayne M Spies Thomas Rammensee Hans-Georg Steinle Alexander |
| |
Institution: | Department of Immunology, Institute for Cell Biology, Eberhard Karls University Tübingen, Auf der Morgenstelle 15, 72076 Tübingen, Germany. |
| |
Abstract: | 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. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|