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Blood, 1 June 2004, Vol. 103, No. 11, pp. 4201-4206.
Prepublished online as a Blood First Edition Paper on December 24, 2003; DOI 10.1182/blood-2003-09-3108.


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Submitted September 10, 2003
Accepted December 14, 2003

A cell surface molecule selectively expressed on murine Natural Interferon Producing Cells that blocks secretion of interferon-alpha

Amanda Blasius, William Vermi, Anne Krug, Fabio Facchetti, Marina Cella, and Marco Colonna*

Pathology and Immmunology, Washington University School of Medicine, St Louis, MO, USA
Pathology, University of Brescia, Brescia, Italy

* Corresponding author; email: mcolonna{at}pathology.wustl.edu.

Natural interferon producing cells (IPC) recognize certain viruses and DNA containing CpG motifs through toll like receptor (TLR) 9, resulting in secretion of IFN-{alpha}, IL-12 and proinflammatory chemokines. Human IPC are found predominantly in inflamed lymph nodes, where they are presumably recruited from the blood to activate both innate and adaptive responses to microbial infections. Demonstrating IPC recruitment in murine infection models has been difficult because multiple antibodies are required to distinguish IPC from other immune cells and very few can be recovered from lymph nodes. Here we describe a mAb that exclusively detects murine IPC in all lymphoid organs under both normal and inflammatory conditions. Using this antibody, we demonstrate that IPC are normally present in the T cell zone of lymph nodes and spleen and that inoculation of peripheral tissues with inflammatory stimuli triggers recruitment of IPC into sentinel lymph nodes, whether the stimuli are able to directly stimulate IPC through TLR or not. Remarkably, we show that incubation of IPC with the antibody in vitro or administration of the antibody in vivo dramatically reduce secretion of IFN-{alpha} in response to CpG DNA without causing IPC depletion. Thus, the antibody identifies an IPC-specific surface molecule that, when engaged, inhibits IFN-{alpha} secretion.


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