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Regulation of Dendritic Cell Migration to the Draining Lymph Node : Impact on T Lymphocyte Traffic and Priming

Alfonso Martín-Fontecha¹, Silvia Sebastiani¹, Uta E. Höpken², Mariagrazia Uguccioni¹, Martin Lipp², Antonio Lanzavecchia¹ and Federica Sallusto¹

¹ Institute for Research in Biomedicine, CH-6500 Bellinzona, Switzerland
² Max Delbrück Center for Molecular Medicine, 13122 Berlin-Buch, Germany

Address correspondence to Alfonso Martín-Fontecha, Institute for Research in Biomedicine, Via Vincenzo Vela 6, CH-6500 Bellinzona, Switzerland. Phone: 41-91-820-0330; Fax: 41-91-820-0305; email: alfonso.martin-fontecha{at}irb.unisi.ch

Antigen-pulsed dendritic cells (DCs) are used as natural adjuvants for vaccination, but the factors that influence the efficacy of this treatment are poorly understood. We investigated the parameters that affect the migration of subcutaneously injected mouse-mature DCs to the draining lymph node. We found that the efficiency of DC migration varied with the number of injected DCs and that CCR7^+/+ DCs migrating to the draining lymph node, but not CCR7^-/- DCs that failed to do so, efficiently induced a rapid increase in lymph node cellularity, which was observed before the onset of T cell proliferation. We also report that DC migration could be increased up to 10-fold by preinjection of inflammatory cytokines that increased the expression of the CCR7 ligand CCL21 in lymphatic endothelial cells. The magnitude and quality of CD4⁺ T cell response was proportional to the number of antigen-carrying DCs that reached the lymph node and could be boosted up to 40-fold by preinjection of tumor necrosis factor that conditioned the tissue for increased DC migration. These results indicate that DC number and tissue inflammation are critical parameters for DC-based vaccination.

Key Words: dendritic cell • T cell priming • CCL21 • migration • dendritic cell–based vaccination

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• McKee, A. S., Dzierszinski, F., Boes, M., Roos, D. S., Pearce, E. J. (2004). Functional Inactivation of Immature Dendritic Cells by the Intracellular Parasite Toxoplasma gondii. J. Immunol. 173: 2632-2640 [Abstract] [Full Text]  
• Yoneyama, H., Matsuno, K., Zhang, Y., Nishiwaki, T., Kitabatake, M., Ueha, S., Narumi, S., Morikawa, S., Ezaki, T., Lu, B., Gerard, C., Ishikawa, S., Matsushima, K. (2004). Evidence for recruitment of plasmacytoid dendritic cell precursors to inflamed lymph nodes through high endothelial venules. Int Immunol 16: 915-928 [Abstract] [Full Text]  
• Kobayashi, H., Miura, S., Nagata, H., Tsuzuki, Y., Hokari, R., Ogino, T., Watanabe, C., Azuma, T., Ishii, H. (2004). In situ demonstration of dendritic cell migration from rat intestine to mesenteric lymph nodes: relationships to maturation and role of chemokines. J. Leukoc. Biol. 75: 434-442 [Abstract] [Full Text]  
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