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International Immunology Advance Access originally published online on September 11, 2006
International Immunology 2006 18(11):1563-1573; doi:10.1093/intimm/dxl089
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© The Japanese Society for Immunology. 2006. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Dendritic cell activating peptides induce distinct cytokine profiles

Gloria Telusma1, Sandip Datta2, Ivan Mihajlov2, Wenxue Ma3, Jianhua Li1,4, Huan Yang1,4, Walter Newman5, Bradley T. Messmer1,6, Boris Minev3, Ingo G. H. Schmidt-Wolf7, Kevin J. Tracey1,4, Nicholas Chiorazzi1,6 and Davorka Messmer1,6,8

1 The Feinstein Institute for Medical Research, North Shore—LIJ Health System, Manhasset, NY 11030, USA
2 Department of Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
3 University of California San Diego, Rebecca and John Moores UCSD Cancer Center, 3855 Health Science Drive, La Jolla, CA 92093, USA
4 Department of Surgery, North Shore University Hospital and Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA
5 Critical Therapeutics Inc., Lexington, MA 04241-3108, USA
6 Department of Medicine, North Shore University Hospital and NYU School of Medicine, 550 First Avenue, New York, NY 10016, USA
7 Department of Internal Medicine, Rheinische Friedrich-Wilhelm Universitaet, Sigmund Freud Strasse 25, Bonn, Germany
8 Present address: Moorse UCSD Cancer Center, 3855 Health Science Drive, La Jolla, CA 92093-0820, USA

Correspondence to: D. Messmer; E-mail: dmessmer{at}ucsd.edu

High-mobility group box 1 protein (HMGB1), a DNA-binding nuclear and cytosolic protein, is a pro-inflammatory cytokine released by monocytes and macrophages. HMGB1 as well as its B box domain induce maturation of human dendritic cells (DCs). This report demonstrates that the B box domain induces phenotypic maturation of murine bone marrow-derived dendritic cells (BM-DCs) as evidenced by increased CD86, CD40 and MHC-II expression. The B box domain enhanced secretion of pro-inflammatory cytokines and chemokines: IL-1ß, IL-2, IL-5, IL-8, IL-12 and tumor necrosis factor (TNF)-{alpha}, but not IL-6 and IL-10. Furthermore, four peptides whose sequences correspond to different regions of HMGB1 induced production of IL-1ß, IL-2 and IL-12 (p70), but not IL-10 and IL-6 in mouse BM-DCs. Interestingly, these peptides differed in their capacity to induce TNF-{alpha}, IL-5, IL-18 and IL-8. B box domain as well as peptide-activated DCs acted as potent stimulators of allogeneic T cells in a mixed leukocyte reaction. DCs exposed to HMGB1 peptides induced proliferation of ovalbumin-specific syngeneic T cells. These DC-activating peptides could serve as an adjuvant in immunotherapeutic or vaccine context and the selective activity of these different peptides suggests a means to customize the functional properties of DCs.

Keywords: cytokines, immune adjuvant, inflammation, necrosis

Transmitting editor: R. A. Flavell


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