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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-Kb promoter. Although MICA functions as a potent activating ligand of mouse NKG2D, H2-Kb-MICA mice appear healthy without aberrations in lymphocyte subsets. However, NKG2D-mediated cytotoxicity of H2-Kb-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-Kb-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.<\/jats:p>","DOI":"10.4049\/jimmunol.175.2.720","type":"journal-article","created":{"date-parts":[[2014,4,22]],"date-time":"2014-04-22T22:40:18Z","timestamp":1398206418000},"page":"720-729","source":"Crossref","is-referenced-by-count":203,"title":["Systemic NKG2D Down-Regulation Impairs NK and CD8 T Cell Responses In Vivo"],"prefix":"10.1093","volume":"175","author":[{"given":"Katrin","family":"Wiemann","sequence":"first","affiliation":[{"name":"Department of Immunology, Institute for Cell Biology, Eberhard Karls University Tu\u0308bingen , Tu\u0308bingen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Willi","family":"Mittru\u0308cker","sequence":"additional","affiliation":[{"name":"Department of Immunology, Max Planck Institute for Infection Biology , Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ute","family":"Feger","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute for Cell Biology, Eberhard Karls University Tu\u0308bingen , Tu\u0308bingen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan A","family":"Welte","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute for Cell Biology, Eberhard Karls University Tu\u0308bingen , Tu\u0308bingen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wayne M","family":"Yokoyama","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Division of Rheumatology, Washington University School of Medicine and Barnes-Jewish Hospital , St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Spies","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Research Center, Clinical Research Division , Seattle, WA 98109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Georg","family":"Rammensee","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute for Cell Biology, Eberhard Karls University Tu\u0308bingen , Tu\u0308bingen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Steinle","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute for Cell Biology, Eberhard Karls University Tu\u0308bingen , Tu\u0308bingen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2005,7,15]]},"reference":[{"key":"2026020212155375600_R1","first-page":"727","volume-title":"Science","year":"1999"},{"key":"2026020212155375600_R2","first-page":"730","volume-title":"Science","year":"1999"},{"key":"2026020212155375600_R3","first-page":"3667","volume-title":"J. 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