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Published 6 September 2005. doi:10.1084/jem.20051035
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 202, Number 5, 687-696
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ARTICLE

Adhesive mechanisms governing interferon-producing cell recruitment into lymph nodes

Thomas G. Diacovo1, Amanda L. Blasius1, Tak W. Mak2,3, Marina Cella1, and Marco Colonna1

1 Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110
2 Advanced Medical Discovery Institute, Ontario Cancer Institute, Department of Medical Biophysics
3 Department of Immunology, University of Toronto, Toronto, Ontario, M5G 2C1, Canada

CORRESPONDENCE Thomas G. Diacovo: td2142{at}columbia.edu

Natural interferon-producing cells (IPCs) are found in peripheral lymph nodes (PLNs), where they support NK cell, T cell, and B cell responses to pathogens. However, their route of entry and the adhesive mechanisms used to gain access to PLNs remain poorly defined. We report that IPCs can enter PLNs via a hematogenous route, which involves a multistep adhesive process, and that transmigration is enhanced by inflammation. Results indicate that L-selectin on IPCs is required for efficient attachment and rolling on high endothelial venules in vivo in both nonstimulated and inflamed PLNs. IPCs, however, also possess functional ligands for E-selectin that contribute to this process only in the latter case. In conjunction with selectin-mediated adhesion, both ß1- and ß2-integrins participate in IPC attachment to the inflamed vessel wall, whereas chemotaxis relies in part on the chemokine receptor CCR5. Identification of the adhesive machinery required for IPC trafficking into PLNs may provide opportunities to regulate immune responses reliant on the activity of these cells.


Abbreviations used: BCECF, 2'7',-bis-(2-carboxyethyl)-5(and 6) carboxyfluorescein; HEV, high endothelial venule; ICAM, intercellular adhesion molecule; IPC, IFN-producing cell; IVM, intravital microscopy; LFA, lymphocyte function-associated antigen; Mtb, Mycobacterium tuberculosis; PLN, peripheral LN; PNAd, peripheral node addressin; PTX, pertussis toxin; RANTES, regulated on activation, normal T cell expressed and secreted; TLR, Toll-like receptor; VCAM, vascular endothelial adhesion molecule.


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