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Blood, 1 August 2005, Vol. 106, No. 3, pp. 978-987.
Prepublished online as a Blood First Edition Paper on April 19, 2005; DOI 10.1182/blood-2004-07-2656.
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Submitted July 13, 2004
Accepted April 4, 2005
TLR3-induced activation of mast cells modulates CD8+ T cell-recruitment
Zane Orinska, Elena Bulanova, Vadim Budagian, Martin Metz, Marcus Maurer, and Silvia Bulfone-Paus*
Deprtment of Immunology and Cell Biology, Research Center Borstel, Borstel, Germany
Department of Dermatology, University of Mainz, Mainz, Germany
Department of Dermatology, University of Mainz, Mainz, Germany; Department of Dermatology and Allergy, University Hospital Charite, Humboldt University Berlin, Berlin, Germany
* Corresponding author; email: sbulfone{at}fz-borstel.de.
Mast cells are known to play an important role in host defense against various pathogens, but their role in viral infection has not been clarified in detail. Double-stranded RNA, synthesised by various types of viruses and mimicked by poly(I:C), is recognized by Toll-like receptor 3 (TLR3). In this study, we demonstrate that poly(I:C) injection in vivo potently stimulates peritoneal mast cells to upregulate a number of different co-stimulatory molecules. Therefore, we examined the expression and the functional significance of TLR3 activation in mast cells. Mast cells express TLR3 on the cell surface and intracellularly. After stimulation of mast cells with poly(I:C) and Newcastle disease virus (NDV), TLR3 is phosphorylated and the expression of key antiviral response cytokines (IFN , ISG15) and chemokines (IP10, RANTES) is upregulated. Interestingly, mast cells activated via TLR3-poly(I:C) potently stimulate CD8+ T cell recruitment. Indeed, mast cell deficient mice (KitW/KitW-v) intraperitoneally injected with poly(I:C) show a decreased CD8+ T cell recruitment, whereas granulocytes normally migrate to the peritoneal cavity. Mast cell-reconstitution of KitW/KitW-v mice normalizes the CD8+ T cell influx. Thus, mast cells stimulated through engagement of TLR3 are potent regulators of CD8+ T cell activities in vitro and in vivo.

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