Regulation of dendritic cell migration to the draining lymph node: impact on T lymphocyte traffic and priming.
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.
MartIn-Fontecha
Alfonso
A
Institute for Research in Biomedicine, Via Vincenzo Vela 6, CH-6500 Bellinzona, Switzerland. alfonso.martin-fontecha@irb.unisi.ch
Sebastiani
Silvia
S
Höpken
Uta E
UE
Uguccioni
Mariagrazia
M
Lipp
Martin
M
Lanzavecchia
Antonio
A
Sallusto
Federica
F
D000818:Animals; D002465:Cell Movement; D017690:Cell Transplantation; D003713:Dendritic Cells / Q000502:physiology*; D005456:Fluorescent Dyes / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C515370:CCR7 protein, human; C515371:Ccr7 protein, mouse; D005456:Fluorescent Dyes; D007375:Interleukin-1; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha