© 2004 by Oxford University Press
© 2004 Oxford University Press
ARTICLE |
Mobilization of Dendritic Cell Precursors Into the Circulation by Administration of MIP-1
in Mice
Affiliations of authors: Department of Molecular Preventive Medicine, School of Medicine, The University of Tokyo, Tokyo, Japan (YZ, HY, YW, SI, SH, KM); Molecular Signaling Section, Laboratory of Host Defense, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (JLG, PM).
Correspondence to: Professor Kouji Matsushima, Department of Molecular Preventive Medicine, School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan (e-mail: koujim{at}m.u-tokyo.ac.jp)
Background: Dendritic cells (DCs) play a central role in immune responses and may be useful adjuvants for tumor vaccine therapy. We previously reported that F4/80–B220–CD11c+ DC precursors expressing the CC chemokine receptors CCR1 and CCR5 are mobilized rapidly into the circulation in mice injected with Propionibacterium acnes and are recruited into inflammatory tissue by macrophage inflammatory protein 1
(MIP-1), which binds to CCR1 and CCR5. Here we investigate the mechanisms of DC precursor mobilization and the antitumor effect of these cells in mice. Methods: Numbers of DC precursors in peripheral blood were determined in P. acnes–treated mice (groups of 10 C57BL/B6 [B6] wild-type mice, CCR1-/- mice, CCR5-/- mice, and B6 mice treated with antibody to MIP-1 or control antibody) and in B6 mice injected with recombinant MIP-1. MIP-1–mobilized DC precursors matured by treatment with granulocyte–macrophage colony-stimulating factor, interleukin 4, and tumor necrosis factor- and pulsed with B16 melanoma lysates were assayed for their ability to confer protective immunity against tumor challenge in vivo and to induce cytotoxic T lymphocytes against B16 tumor cells in vitro. Results: The recruitment of DC precursors into the circulation by P. acnes administration was higher in B6 mice (12.6%, 95% confidence interval [CI] = 9.1% to 16.1%) than in CCR1-/- (9.0%, 95% CI = 7.5% to 10.5%), CCR5-/- (6.3%, 95% CI = 5.2% to 7.3%), or anti-MIP-1 antibody–treated (6.6%, 95% CI = 5.7% to 7.5%) mice. Injection of MIP-1 also mobilized DC precursors into the circulation (13.1%, 95% CI = 10.8% to 15.6%). Matured MIP-1–mobilized-DC precursors pulsed with B16 tumor lysates elicited B16-specific antitumor immunity in vitro and in vivo. Conclusions: MIP-1 and its receptors are important in recruiting DC precursors into the circulation. DC precursors mobilized rapidly by MIP-1 may provide sufficient useful DC precursors for DC-based vaccination in cancer treatment.
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