{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T21:25:14Z","timestamp":1791149114129,"version":"4.1.0"},"reference-count":43,"publisher":"Rockefeller University Press","issue":"12","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2005,6,20]]},"abstract":"<jats:p>The dynamic regulation of ligand binding is considered crucial for integrin function. However, the importance of activity regulation for integrin function in vivo is largely unknown. Here, we have applied gene targeting to delete the GFFKR sequence of the lymphocyte function-associated antigen\u20131 (LFA-1) \u03b1L subunit cytoplasmic domain in mouse germline. Lymphocytes from Lfa-1d\/d mutant mice showed constitutive activation of LFA-1\u2013mediated cell adhesion and impaired de-adhesion from intercellular adhesion molecule-1 that resulted in defective cell migration. In contrast, signaling through LFA-1 was not affected in Lfa-1d\/d cells. T cell activation by superantigen-loaded and allogeneic APCs, cytotoxic T cell activity, T-dependent humoral immune responses, and neutrophil recruitment during aseptic peritonitis were impaired in Lfa-1d\/d mice. Thus, deactivation of LFA-1 and disassembly of LFA-1\u2013mediated cell contacts seem to be vital for the generation of normal immune responses.<\/jats:p>","DOI":"10.1084\/jem.20041850","type":"journal-article","created":{"date-parts":[[2005,6,15]],"date-time":"2005-06-15T03:34:06Z","timestamp":1118806446000},"page":"1987-1998","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":106,"title":["Importance of integrin LFA-1 deactivation for the generation of immune responses"],"prefix":"10.1084","volume":"201","author":[{"given":"Monika","family":"Semmrich","sequence":"first","affiliation":[{"name":"1Department of Surgery, Immunology, and Hygiene, Technische Universita\u0308t Mu\u0308nchen, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Smith","sequence":"additional","affiliation":[{"name":"3Cancer Research UK, London Research Institute, London WC2A 3PX, England, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolin","family":"Feterowski","sequence":"additional","affiliation":[{"name":"1Department of Surgery, Immunology, and Hygiene, Technische Universita\u0308t Mu\u0308nchen, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Beer","sequence":"additional","affiliation":[{"name":"1Department of Surgery, Immunology, and Hygiene, Technische Universita\u0308t Mu\u0308nchen, 81675 Munich, Germany"},{"name":"4Institute of Medical Microbiology, Universita\u0308t Du\u0308sseldorf, 40225 Du\u0308sseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Britta","family":"Engelhardt","sequence":"additional","affiliation":[{"name":"5Theodor Kocher Institute, University of Bern, CH-3012 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk H.","family":"Busch","sequence":"additional","affiliation":[{"name":"2Institute of Medical Microbiology, Immunology, and Hygiene, Technische Universita\u0308t Mu\u0308nchen, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernadett","family":"Bartsch","sequence":"additional","affiliation":[{"name":"1Department of Surgery, Immunology, and Hygiene, Technische Universita\u0308t Mu\u0308nchen, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Laschinger","sequence":"additional","affiliation":[{"name":"3Cancer Research UK, London Research Institute, London WC2A 3PX, England, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Hogg","sequence":"additional","affiliation":[{"name":"3Cancer Research UK, London Research Institute, London WC2A 3PX, England, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Pfeffer","sequence":"additional","affiliation":[{"name":"4Institute of Medical Microbiology, Universita\u0308t Du\u0308sseldorf, 40225 Du\u0308sseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Holzmann","sequence":"additional","affiliation":[{"name":"1Department of Surgery, Immunology, and Hygiene, Technische Universita\u0308t Mu\u0308nchen, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2005,6,13]]},"reference":[{"key":"2023072512540626300_BIB1","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/S0092-8674(02)00971-6","volume":"110","year":"2002","journal-title":"Cell."},{"key":"2023072512540626300_BIB2","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1161\/hh1501.094874","volume":"89","year":"2001","journal-title":"Circ. 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