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Blood, 15 January 2007, Vol. 109, No. 2, pp. 661-669.
Prepublished online as a Blood First Edition Paper on September 26, 2006; DOI 10.1182/blood-2005-12-023044.


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Submitted December 5, 2005
Accepted August 1, 2006

Active MAC-1 (CD11b/CD18) on DC is inhibitory for full T cell activation

Georg Varga, Sandra Balkow, Martin K Wild, Andrea Stadtbaeumer, Mathias Krummen, Tobias Rothoeft, Tetsuya Higuchi, Stefan Beissert, Klaus Wethmar, Karin Scharffetter-Kochanek, Dietmar Vestweber, and Stephan Grabbe*

Department of Dermatology, University of Muenster, Germany
Center for Molecular Biology of Inflammation, University of Muenster, Germany
Max-Delbrueck-Center for Molecular Medicine, Berlin-Buch, Germany
Department of Dermatology, University of Ulm, Germany
Max-Planck-Institute for Molecular Biomedicine, Muenster, Germany
Department of Dermatology, University of Essen, Germany

* Corresponding author; email: grabbe{at}med.uni-essen.de.

{beta}2 integrins are important for transendothelial migration of leukocytes as well as for T cell activation during antigen presentation. Despite abundant expression of {beta}2 integrins on APC, their functional relevance for antigen presentation is completely unclear. We show here that DC from CD18-deficient mice, which lack all functional {beta}2 integrins, have no defect in antigen presentation. Moreover, DC from normal mice express inactive {beta}2 integrins that do not become activated upon contact with T cells, at least in vitro. Pharmacological activation of {beta}2 integrins on DC results in a significant reduction of their T cell activating capacity. This effect is mediated by Mac-1 (CD11b/CD18) on DC since it could be reversed via blocking antibodies against CD18 and CD11b. Furthermore, the antigen presenting capacity of macrophages, that express constitutively active {beta}2 integrins, is significantly enhanced upon Mac-1 blockade. We therefore conclude that active CD11b/CD18 (Mac-1) on APC directly inhibits T cell activation.


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