The Journal of Experimental Medicine
Torrey Pines Biolabs
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 13 June 2005 doi:10.1084/jem.20041850
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 201, Number 12, 1987-1998
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 1741K)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Semmrich, M.
Right arrow Articles by Holzmann, B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Semmrich, M.
Right arrow Articles by Holzmann, B.
Related Collections
Right arrowRelated Article
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

ARTICLE

 Importance of integrin LFA-1 deactivation for the generation of immune responses

Monika Semmrich1, Andrew Smith3, Carolin Feterowski1, Sandra Beer1,4, Britta Engelhardt5, Dirk H. Busch2, Bernadett Bartsch1, Melanie Laschinger3, Nancy Hogg3, Klaus Pfeffer4, and Bernhard Holzmann1

1 Department of Surgery, Immunology, and Hygiene, Technische Universität München, 81675 Munich, Germany
2 Institute of Medical Microbiology, Immunology, and Hygiene, Technische Universität München, 81675 Munich, Germany
3 Cancer Research UK, London Research Institute, London WC2A 3PX, England, UK
4 Institute of Medical Microbiology, Universität Düsseldorf, 40225 Düsseldorf, Germany
5 Theodor Kocher Institute, University of Bern, CH-3012 Bern, Switzerland

CORRESPONDENCE Bernhard Holzmann: holzmann{at}nt1.chir.med.tu-muenchen.de

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–1 (LFA-1) {alpha}L subunit cytoplasmic domain in mouse germline. Lymphocytes from Lfa-1d/d mutant mice showed constitutive activation of LFA-1–mediated 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–mediated cell contacts seem to be vital for the generation of normal immune responses.

Abbreviations used: ICAM, intercellular adhesion molecule; LFA-1, lymphocyte function- associated antigen-1; SEB, Staphylococcal enterotoxin B; VCAM, vascular cell adhesion molecule.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?

Related Article

Lymphocytes that can't let go
Heather L. Van Epps
J. Exp. Med. 2005 201: 1867. [Full Text] [PDF]



This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS