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

Semmrich, Monika LU ; Smith, Andrew; Feterowski, Carolin; Beer, Sandra; Engelhardt, Britta; Busch, Dirk H; Bartsch, Bernadett; Laschinger, Melanie; Hogg, Nancy and Pfeffer, Klaus, et al. (2005) In Journal of Experimental Medicine 201(12). p.1987-1998
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... (More)
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. (Less)
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publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Experimental Medicine
volume
201
issue
12
pages
1987 - 1998
publisher
Rockefeller University Press
external identifiers
  • pmid:15955836
  • scopus:22344438374
ISSN
1540-9538
DOI
10.1084/jem.20041850
language
English
LU publication?
no
id
2bd1ab59-4b5f-4a74-b3b1-db02848a3441 (old id 1134247)
date added to LUP
2008-06-18 08:35:42
date last changed
2017-07-30 04:45:36
@article{2bd1ab59-4b5f-4a74-b3b1-db02848a3441,
  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.},
  author       = {Semmrich, Monika and Smith, Andrew and Feterowski, Carolin and Beer, Sandra and Engelhardt, Britta and Busch, Dirk H and Bartsch, Bernadett and Laschinger, Melanie and Hogg, Nancy and Pfeffer, Klaus and Holzmann, Bernhard},
  issn         = {1540-9538},
  language     = {eng},
  number       = {12},
  pages        = {1987--1998},
  publisher    = {Rockefeller University Press},
  series       = {Journal of Experimental Medicine},
  title        = {Importance of integrin LFA-1 deactivation for the generation of immune responses},
  url          = {http://dx.doi.org/10.1084/jem.20041850},
  volume       = {201},
  year         = {2005},
}