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,
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Experimental Transplantation and Immunology Branch, National Cancer Institute, Bethesda, MD 20892; and
Science Application International Corp. and
Laboratory of Molecular Immunoregulation, National Cancer Institute, Frederick, MD 21702
Chemokine receptors are differentially expressed on immature and
mature dendritic cells (DC). Herein, we demonstrate for the first time
that murine antimicrobial peptides 
-defensins 2 and 3 bind murine
CCR6, similarly to inflammatory chemokine macrophage-inflammatory
protein 3
, and they chemoattract bone marrow-derived immature, but
not mature DC. Using various chemokines or defensins fused with
nonimmunogenic tumor Ags, we studied their capacity to delivery Ags to
subsets of immune cells to elicit antitumor immunity. We demonstrate
that DNA immunizations with fusion constructs with -defensin 2 or
inflammatory chemokines that target immature DC, but not homeostatic
chemokines secondary lymphoid tissue chemokine, CCL21, or stromal
cell-derived factor 1, CXCL12, which chemoattract mature DC,
elicit humoral, protective, and therapeutic immunity against two
different syngeneic lymphomas.
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D. Proud, S. P. Sanders, and S. Wiehler Human Rhinovirus Infection Induces Airway Epithelial Cell Production of Human {beta}-Defensin 2 Both In Vitro and In Vivo J. Immunol., April 1, 2004; 172(7): 4637 - 4645. [Abstract] [Full Text] [PDF]
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K. Tschoep, T. C. Manning, H. Harlin, C. George, M. Johnson, and T. F. Gajewski Disparate functions of immature and mature human myeloid dendritic cells: implications for dendritic cell-based vaccines J. Leukoc. Biol., July 1, 2003; 74(1): 69 - 80. [Abstract] [Full Text] [PDF]
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 A. Biragyn, P. A. Ruffini, C. A. Leifer, E. Klyushnenkova, A. Shakhov, O. Chertov, A. K. Shirakawa, J. M. Farber, D. M. Segal, J. J. Oppenheim, et al. Toll-Like Receptor 4-Dependent Activation of Dendritic Cells by beta -Defensin 2 Science, November 1, 2002; 298(5595): 1025 - 1029. [Abstract] [Full Text] [PDF]
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A. Biragyn, I. M. Belyakov, Y.-H. Chow, D. S. Dimitrov, J. A. Berzofsky, and L. W. Kwak DNA vaccines encoding human immunodeficiency virus-1 glycoprotein 120 fusions with proinflammatory chemoattractants induce systemic and mucosal immune responses Blood, July 30, 2002; 100(4): 1153 - 1159. [Abstract] [Full Text] [PDF]
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