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

Research output: Contribution to journalArticle

Abstract

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-1(d/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-1(d/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-1(d/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.

Details

Authors
  • Monika Semmrich
  • Andrew Smith
  • Carolin Feterowski
  • Sandra Beer
  • Britta Engelhardt
  • Dirk H Busch
  • Bernadett Bartsch
  • Melanie Laschinger
  • Nancy Hogg
  • Klaus Pfeffer
  • Bernhard Holzmann
External organisations
  • External Organization - Unknown
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Immunology in the medical area
Original languageEnglish
Pages (from-to)1987-1998
JournalJournal of Experimental Medicine
Volume201
Issue number12
Publication statusPublished - 2005
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes