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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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.

Detaljer

Författare
  • Monika Semmrich
  • Andrew Smith
  • Carolin Feterowski
  • Sandra Beer
  • Britta Engelhardt
  • Dirk H Busch
  • Bernadett Bartsch
  • Melanie Laschinger
  • Nancy Hogg
  • Klaus Pfeffer
  • Bernhard Holzmann
Externa organisationer
  • Technical University of Munich
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Immunologi inom det medicinska området
Originalspråkengelska
Sidor (från-till)1987-1998
TidskriftJournal of Experimental Medicine
Volym201
Utgåva nummer12
StatusPublished - 2005
PublikationskategoriForskning
Peer review utfördJa
Externt publiceradJa