The Journal of Experimental Medicine
StemCell Technologies
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Published 18 November 2002. doi:10.1084/jem.20021466
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© Rockefeller University Press, 0022-1007/2002/11/1393/ $5.00
The Journal of Experimental Medicine, Volume 196, Number 10, November 18, 2002 1393-1398

Brief Definitive Report

 Cross-linking the B7 Family Molecule B7-DC Directly Activates Immune Functions of Dendritic Cells

Loc T. Nguyen1, Suresh Radhakrishnan1, Bogoljub Ciric1, Koji Tamada1, Tahiro Shin2, Drew M. Pardoll2, Lieping Chen1, Moses Rodriguez1,3 and Larry R. Pease1

1 Department of Immunology, Mayo Medical and Graduate Schools, Mayo Clinic, Rochester, MN 55905
2 Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21231
3 Department of Neurology, Mayo Medical and Graduate Schools, Mayo Clinic, Rochester, MN 55905

Address correspondence to Larry R. Pease, Department of Immunology, Mayo Medical and Graduate Schools, 200 First St. SW, Rochester, MN 55905. Phone: 507-284-8177; Fax: 507-266-0981; E-mail: pease.larry{at}mayo.edu

B7-DC molecules are known to function as ligands on antigen-presenting cells (APCs), enhancing T cell activation. In this study, cross-linking B7-DC with the monoclonal antibody sHIgM12 directly potentiates dendritic cell (DC) function by enhancing DC presentation of major histocompatibility complex–peptide complexes, promoting DC survival; and increasing secretion of interleukin (IL)-12p70, a key T helper cell type 1 promoting cytokine. Furthermore, ex vivo treatment of DCs or systemic treatment of mice with sHIgM12 increases the number of transplanted DCs that reach draining lymph nodes and increases the ability of lymph node APCs to activate naive T cells. Systemic administration of the antibody has an equivalent effect on DCs transferred at a distant site. These findings implicate B7-DC expressed on DCs in bidirectional communication. In addition to the established costimulatory and inhibitory functions associated with B7-DC, this molecule can also function as a conduit for extracellular signals to DCs modifying DC functions.

Key Words: dendritic cells • costimulation • B7 superfamily • B7-DC • IL-12


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