Importance of integrin LFA-1 deactivation for the generation of immune responses.
J Exp Med
; 201(12): 1987-98, 2005 Jun 20.
Article
in En
| MEDLINE
| ID: mdl-15955836
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cell Adhesion
/
Lymphocyte Function-Associated Antigen-1
/
Protein Subunits
/
Immunity, Cellular
/
Antibody Formation
Limits:
Animals
/
Humans
Language:
En
Journal:
J Exp Med
Year:
2005
Document type:
Article
Affiliation country:
Germany
Publication country:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA