Skip Navigation



International Immunology Advance Access published online on November 27, 2009
International Immunology, doi:10.1093/intimm/dxp111
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplementary Data
Right arrow All Versions of this Article:
22/1/35    most recent
dxp111v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Hüser, N.
Right arrow Articles by Laschinger, M.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hüser, N.
Right arrow Articles by Laschinger, M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Japanese Society for Immunology. 2009. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Intact LFA-1 deactivation promotes T-cell activation and rejection of cardiac allograft

Norbert Hüser1,*, Annette Fasan1,*, Monika Semmrich1,2, Patricia Schmidbauer1, Bernhard Holzmann1 and Melanie Laschinger1

1 Department of Surgery, Technische Universität München, Ismaninger Strasse 22, 81675 Munich, Germany
2 Present address: Immunology Section, Department of Cell and Molecular Biology, Lund University, 22184 Lund, Sweden

Correspondence to: M. Laschinger; E-mail: laschinger{at}chir.med.tu-muenchen.de

Leucocyte function-associated antigen-1 (LFA-1) is known to be involved in immune reactions leading to allograft rejection. The role of deactivating LFA-1 in this context has not been investigated yet, although it is accepted that regulating LFA-1 activity is essential for T-cell function. Expressing LFA-1 locked in an active state in mice (LFA-1d/d) allowed us to investigate the in vivo function of LFA-1 deactivation for allograft rejection in a model of heterotopic cardiac transplantation. We provide in vivo evidence that regulating LFA-1 activity from an active to an inactive state controls antigen-specific priming and proliferation of T cells in response to allogeneic stimuli. Consequently, defective LFA-1 deactivation significantly prolonged cardiac allograft survival. Furthermore, reduced numbers of alloantigen-specific T cells and non-allo-specific innate immune cells within allografts of LFA-1d/d recipients indicate that expression of active LFA-1 impairs inflammatory responses involving all major leucocyte subpopulations. Taken together, our in vivo data suggest that LFA-1 deactivation is important for the formation of inflammatory lesions and rejection of cardiac allografts. Thus, the dynamic regulation of LFA-1 activity, rather than the mere presence of LFA-1, appears to contribute to the control of immune reactions inducing allogeneic transplant rejection.

Keywords: inflammation, integrin, T-cell proliferation, transplantation

* These authors contributed equally to this study.

Transmitting editor: T. Hunig

Received 27 May 2009, accepted 29 October 2009.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.