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Blood, 1 April 2006, Vol. 107, No. 7, pp. 2821-2829.
Prepublished online as a Blood First Edition Paper on November 29, 2005; DOI 10.1182/blood-2005-06-2265.


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Submitted June 7, 2005
Accepted November 20, 2005

SLAM/SLAM interactions inhibit CD40-induced production of inflammatory cytokines in monocyte derived dendritic cells

Bence Rethi, Peter Gogolak, Istvan Szatmari, Agota Veres, Erika Erdos, Laszlo Nagy, Eva Rajnavolgyi, Cox Terhorst, and Arpad Lanyi*

Institute of Immunology, University of Debrecen Medical and Health Science Center, Debrecen, Hungary
Department of Biochemistry and Molecular Biology, University of Debrecen Medical and Health Science Center, Debrecen, Hungary
Division of Immunology, Beth Israel Deaconess Medical Center, Boston, USA

* Corresponding author; email: alanyi{at}dote.hu.

SLAM (Signaling Lymphocyte Activation Molecule, CD150 or SLAMF1) is a self-ligand receptor on the surface of activated T- and B-lymphocytes, macrophages and dendritic cells (DCs). Here we examine the effect of SLAM/SLAM interactions on CD40L-induced CD40 signaling pathways in human DCs. CD40L-expressing L929 cells induced DCs to produce IL-6, TNF-{alpha} and IL-12, which was strongly inhibited by co-expression of SLAM on the surface of the L929 cells. Similarly, transfection of DCs with SLAM strongly reduced CD40L-induced IL-12 production. Furthermore, the negative effect of SLAM/SLAM interactions on CD40L-induced DC activation was also detected in the presence of LPS. LPS-induced IL-12 secretion, however, was not inhibited by SLAM-engagement. CD40L-activated DCs affected by exposure to SLAM/SLAM engagement were impaired in their ability to induce differentiation of naive T lymphocytes into IFN-{gamma} producing Th1 effector cells. These inhibitory effects were not the result of a general unresponsiveness of DCs to CD40L, as SLAM/SLAM interactions did not prevent CD40L-induced up-regulation of CD83, CD86 or HLA-DQ on the surface of DCs. Taken together, the results indicate that SLAM/SLAM interactions inhibit CD40-induced signal transduction in monocyte derived dendritic cells, an effect that was not detectable in earlier studies using anti-SLAM monoclonal antibodies.


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